Basic Genetics Volume 1 - Module 1

SUMMARY Class 1The origins of ideas about heredity 7

Blanche Christine Bitner-Mathé

Class 2–Cell Division I - Mitosis and the Cell Cycle 21

Patrick Goltsman Moreno

Class 3–Cell Division II - Meiosis 35

Patrick Goltsman Moreno

Class 4--Mendelism: the Birth of Genetics 53

Blanche Christine Bitner-Mathé

Class 5–Mendel's Work: Unraveling the Second Law 75

Blanche Christine Bitner-Mathé

Class 6–The chromosomal theory of inheritance and the discovery

two sex chromosomes 93
Blanche Christine Bitner-Mathé

Class 7Chromosomes, genes, DNA:

a current view of Mendelian factors 117
Blanche Christine Bitner-Mathé

Class 8–From gene to phenotype 137

Blanche Christine Bitner-Mathé

Class 9–Introduction to Human Genetics:

analysis of monogenic characteristics 161
Blanche Christine Bitner-Mathé

Lesson 10–Practical activity 179

Patrick Goltsman Moreno

Template 187
References 213
 The origins of ideas
about heredity 1
By the end of this class, you should be able to:
To understand some of the pre-Mendelian ideas to explain
the heredity.
Understanding that Genetics is an essentially
experimental that owes its rapid advancement to the use of
scientific procedures.
Basic Genetics | The origins of ideas about heredity

The phrase 'Nothing in Biology makes sense except in the light of'

"evolution" by Th. Dobzhansky is already familiar to you. Regarding it, Moore,

in 1986, he commented: "But there is something more fundamental from where

all the main concepts of Biology derive from Genetics.

INTRODUCTION This is our first class on Genetics. You have heard about it several times.
from this theme in the subjects Great Themes in Biology and Diversity of
Living Beings. One must also listen a lot in the media about the importance of advancements.

from Genetics to our society. It is to be expected that there will be a lot of discussion

in Genetics; as Moore pointed out, this science is at the base of

understanding of various areas of Biology.
But do you really understand the subject of study of Genetics? In this
course, we will take a trip to the past and follow the steps that
they led to the construction of our knowledge about nature and transmission
from biological inheritance. This strategy is based on the article Science as a way
of knowing - Genetics, published by Moore in 1986 in the American journal
Zoologist (Volume 26: 573-747). Although historically the objective of this
the discipline does not include the discovery of the nature of the gene, that is, that DNA

it is the genetic material, we will seek, when appropriate, to complement

the understanding of classical genetic analyses in the light of the fundamentals of

Molecular Biology.
We call Genetics the science that studies the nature of genes and the mechanisms.
of biological inheritance. Genetics is one of the fields of knowledge that most
developed in the last century. It is incredible to imagine that until the 20th century much

little was known about the nature of heredity and that at this beginning of the century
We are surrounded by the advances of this science.
Although the curiosity about understanding the processes that result in
the transmission of biological inheritance dates back to around 400 BC, it can be said

Genetic science began in 1865, with the work of Gregor Mendel,

an Austrian monk who formulated the fundamental laws of inheritance.
However,hisworkwasonlydiscoveredbythescientificcommunityin1900,
andfromtheretheeffortandcreativityofmanyresearchers,associatedwitha
modelofscientificmethodology,allowedgreatadvancesinunderstanding
two events by which the factors of Mendel, which we now call genes,
[Link]

from "factors" for the identification of DNA as the chemical basis of inheritance.

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This knowledge has generated technology that has been enabling the manipulation of the material.

genetic, expanding our view of how genes work, how they can
to be detected, modified, or corrected.
Seebelowsomeexamplesoftheapplicationoftheadvancementsachieved
through Genetics in the last three decades of the 20th century. It is not necessary to be a

geneticists for having heard of them, as they are in our daily lives, being
relevant to many aspects of human life and society, including
health, food production, and legal issues.

1976 - The first engineering company was created 1983 - The first gene is mapped in the USA
genetics, the Genetch, which produced the first related to a disease, a marker for the
human protein in a genetically modified bacterium Huntington's disease is found on chromosome
modified and, in 1982, launched the first 4. The study allowed for the development of a
drug produced by Genetic Engineering, the diagnostic test.
human insulin.

1985 - The British Alec Jeffrey publishes an article 1986 - Genetically modified tobacco plants
that describes the identification technique that remained modified to become resistant to
known as "fingerprint" by DNA, herbicides are tested in the field for the first time
which allowed for more precise elucidation of crimes times, in the USA and France.
and paternity tests.

1990 - Gene therapy is used for the first time 1994 - Release of the Favr Savr tomato, the first
once, successfully, in a four-year-old girl genetically modified food whose sale
with a type of deficiency in the immune system is approved by the FDA (Food and Drug Administration)
called ADA. food from the USA.

1996 - Birth of the sheep Dolly, first 2000– Researchers from the public consortium
cloned mammal from a cell of a Human Genome Project and the private company
adult animal by the Roslin Institute (Scotland) and American company Celera announces the draft of
by the company PPL Therapeutics. Dolly died of humangenome,whichwouldbepublishedinFebruary
premature aging in February 2003. from 2001.
In Brazil, researchers announce the seqüen-
the genome sequencing of the bacterium Xylella fastidiosa,
causative agent of yellow disease in citrus.

Source: Folha de S. Paulo, special 1953 DNA 2003 – The Helix of the Millennium, pages 4 and 5. Article produced by
Luisa Massarani (journalist) and Fábio Gouveia (biologist), from the Museum of Life/Oswaldo Cruz House/Fiocruz and Ildeu of

Castro Moreira, professor of Physics and History of Science at UFRJ.

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 Basic Genetics | The Origins of Ideas about Heredity

SO, SHALL WE GO BACK IN TIME?

The curiosity about how characteristics are transmitted

generations after generations is very old. Already in Greece, around 400 B.C.
thephilosopherHippocrates,consideredtheFatherofMedicine,proposedthehypothesisof

pangenesis to explain the transmission of characteristics between generations.

Hippocrates admitted that heredity was based on the production of
particles all over the body and in the transmission of these particles
for the offspring at the moment of conception. Note that in this hypothesis
the concept of heredity of acquired characteristics is embedded,
what was taken up again by Lamarck much later.

! Aristotle (384-322 B.C.), in his book Generation of Animals, that

it deals with issues of heredity and development, discussed the
Inmanyfieldsofscience-
it is necessary to know the the hypothesis of pangenesis proposed by Hippocrates did not consider that
embryology of ideas: ours
modern vision can only be this would be a good explanation for the transmission of inheritance. Among the
completely compre-
faded and judged if we arguments to reject the hypothesis of pangenesis, Aristotle includes:
understand the reasons that
we need to think like us
we think. One can observe similarities between parents and children that are not limited to
J. R. Baker
body structure, such as voice or the way of [Link] characteristics
non-structural could produce such particles for your
transmission?
Certain children seemed to inherit characteristics from remote ancestors;
Mutilated individuals could produce perfect offspring;
4. If the father and mother produce precursor particles for the entire body, the

Shouldn't descendants have two heads, two legs, etc.?

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 According to Aristotle, there should be a physical basis for the
heredity in the semen produced by the parents. He questions: "Why
not directly admitting that semen... originates from blood and flesh, instead
to affirm that semen is both blood and flesh itself?
Although it may not seem so, the contribution of Hippocrates and Aristotle

it was a great beginning. Hippocrates was able to identify a problem

scientist: how is the transmission of characteristics between generations carried out?

This is possibly the most difficult step of all for progress.

knowledge. He also proposed an explanatory hypothesis and wrote it down.
in an understandable manner.
Aristotle also proposed a hypothesis to explain the
heredity which, although vague, was fundamental to all work
posterior in the area. This idea allowed for the cessation of attributing to Renaissance
Literary movement,
heredity a supernatural or emotional basis and if it were to pass on
artistic and scientific
think of it as the result of the transmission of some type of substance that was verified in us
15th and 16th centuries and
by the countries.
that was based on
During the Middle Ages, the interest in scientific issues large part, in
imitation
it practically ceased in the Western world. It was the period when the Church da Antigüidade.

exercised hegemony over human thought. With ARBIRTH,

the interest returns, observation and experimentation start to be applied
systematically in an attempt to understand nature. For
we understand the advances of Genetics from this resumption of
scientific investigation, we will need to have an idea of how it evolved
our way of doing and thinking about science.

THE ORIGINS OF SCIENCE

FRANCISBACON
You have already been introduced to the Philosophy of Science in the class about (1561-1626)
The Historical Development of Evolutionism in Major Themes Lord Chancellor of
England, wrote
of Biology. But since this is an important subject for you the book Instauratio
Magnaem 1620
follow the construction of knowledge in the field of Genetics, let's where you described your
ideas on how to make
revisit this story. science.
According to scholars of the Philosophy of Science,RANCISBACON

was one of the main responsible for the scientific revolution and the
organization of the scientific method. Between 1606 and 1626, Bacon published
!
a series of books that defended empirical science as the only
Empirical evidence is infor-
appropriate path to test hypotheses and criticized severely obtained from
from direct observation or
the classic habit of starting an investigation with a point of indirect of nature or
view accepted as truth and deduce, from there, the consequences. of experiments.

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Basic Genetics | The origins of ideas about heredity

Your suggestion was that one should start from the known facts related to
with some natural phenomenon and try to formulate general principles that
they explained these facts. This logical reasoning method of starting
Going from the particular to the general is known as induction.
In the centuries that followed Bacon, many other philosophers of
science contributed to our current view of science. The procedure
predicted by Bacon evolved into the so-called hypothetical method
deductive. In this conception, a scientific study begins with observation
D AV I D H U M E
or experimentation of some natural phenomenon. Provisional hypotheses are
1 7 11 - 1 7 7 6
Philosopher and historian.
formulated to explain such a phenomenon and, based on these hypotheses,
deductions are made that allow them to be tested.
The view that scientific explanations are derived generalizations
a series of observations is called positivism. This view has undergone
various questions since the 17th century, but it was only in the mid
of the 18th century that the Scottish philosopher DAVIDHUMEpointed a serious
problem in the induction of generalizations. According to him, the only guarantee

What is there for the success of the inductive method is its past success;
A next observation can undermine the generalization.
The most well-known attempt to solve this paradox was the
Austrian philosopherARLPOPPERAccording to your view, scientists
they really make hypotheses about the nature of the world, sometimes by
K A R L R A I M U N D by means of inductive generalizations, and then submit the hypotheses to
POPPER
(1902-1994) rigorous tests. These tests, however, are not attempts to prove
Philosopher of science. a particular idea, but rather attempts to deny them. That example
classic: after observing thousands of swans, one can generalize that all
the swans are white, but a generalization will only be truly valid
if we could observe all the swans that exist, have existed, and will exist.
The appearance of a black swan would undermine the generalization. That is,
although one cannot verify if all swans are white, upon finding
A swan that is not white can refute this proposal.

!
Hume and Popper are among
the most important philosophers
ofscience.

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 The fragment below was extracted from the text Reflections on
Science and its Teaching, by Prof. José Mariano Amabis, from the Department
from the Biology Department of USP. It summarizes the current view of how it takes place

scientific research

...Once the problem is identified, the researcher uses all their

!
creativecapacitytoproposeaprovisionalexplanationforhim.
This explanation is nothing more than a guess about why the To get to know a little
more about the procedure
contradiction between prevailing knowledge and fact. This guess is the scientific in a well-
hypothesis. A scientific hypothesis, however, is not a creation of humor, read, by Rubem
Alves, Philosophy of Science:
start from scratch. In its development, the researcher makes use of the introduction to the game and its
current theories related to the issue at hand, gathering, rules. 18th ed., São Paulo:
Brasiliense, 1993.
analyzing and interpreting all available information about the
subject. It can be said that during the formulation of a hypothesis
there is an induction process.

The hypothesis or provisional hypotheses are then submitted to tests.

that offer the most severe conditions for criticism. But the only
possible tests are those that, eventually, may show that
the hypothesis is false. There is no way in science to show that
ahypothesisiscorrect,[Link],scientifichypotheses
they credential falsifiability tests. In this type of test, are
made deductions from the hypothesis, that is, imagined situations
in which, if the hypothesis is true (although it cannot be proven
that she may be), there will be one or more specific consequences.
The imagined situations must provide all the conditions for
if the hypothesis is not correct, the forecast does not confirm and,
thus, the hypothesis is refuted.

And if the hypothesis is not refuted? Strictly speaking, we must say

that the hypothesis was not rejected or refuted, and never that it was
confirmed, because, as we saw, it is not possible to validate a hypothesis
positively, no matter how much rigor and control have been used
in your test. This means that in science, we can be sure.
when we are wrong, but we can never be sure of
we are right. Thus, scientific knowledge and the results
insciencetheyshouldnotbeacceptedasdefinitiveandunquestionable;
an explanation in science is accepted as long as we have no reasons
to doubt her, that is, as long as it is 'true' above
of any suspicion.

...These changes in the perspective of how scientists really

theyleadustoanimportantreinterpretationofrelationships
between theories and data. We are obliged to make a clear separation.
defined between the theoretical world and the world of empirical data.
This creates a conception of science that is circular rather than linear.

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Basic Genetics | The origins of ideas about heredity

She involves distinct but parallel worlds (the theoretical world

which reside in the theory and empirical world of observations, linked
through a feedback process of hypothesis testing.

Theories are ideas or models of how the world works. We

we work within a strictly theoretical world, deducing
what consequences should occur from the assumptions and
premises of the model; we then test the validity of the model
comparing the forecasts against the real world. Once that
model provides predictions that match what actually
weobserve,[Link]
the model fails to correctly predict reality, we alter it
the model or we try to develop a better one. Science, in other
words, it is a feedback process: it learns from
your own mistakes. Your behavior is Darwinian, in the sense
that only successful theories survive.

Darwin's attempt to explain inheritance

BIOLOGICAL

In the class Evolution: a theory created 150 years ago is still relevant,
CHARLES disciplineBig Themes in Biology, you had a first contact
R O B E RT D A RW I N
(1809-1882) with the ideas ofDARWINabout biological evolution. Now we will see that
he was also the one who provided us with one of the first examples of use
English naturalist,
published its most from induction in the formulation of a hypothesis aiming to understand the
famous book,
Ontheoriginof hereditariedade.
species, in 1859.
Understand the laws of transmission of biological inheritance and

the emergence of new variants was a fundamental step for the

Darwin's theory of evolution through natural selection. At the time,
most people in the West believed that each organism
had been created separately by the Judeo-Christian God and that the
variations among individuals of the same species would be random and caused
mainly due to environmental differences. Darwin, however, was
convinced that heredity was a general phenomenon, quite
necessary and important.
Your attempt to understand heredity resulted in
the variation of animals and plants
under domestication (1868), where he gathered a large amount
amount of information, seeking to understand the possible origin of
animals and plants domesticated from wild ancestors.

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Darwin admitted that the same factors involved in artificial selection
about hereditary variations, which led to rapid development
of domestic species with favorable characteristics,
they should explain the slow natural selection responsible for the origin of the

species.
For the development of his book, Darwin relied on experiments
that he himself carried out with plants and animals, mainly pigeons,
and in the survey on the results of other researchers.

Figure 1.1: From a lineage of wild pigeons, a great variety

The pigeons with distinct morphologies were obtained through selection in a few generations.
In Darwin's time, the process of crossing and selection was carried out without the
knowledge of the principles of Mendelian inheritance.

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Basic Genetics | The origins of ideas about heredity

After a systematic and extensive information gathering work

about heredity, Darwin was able to draw some observations
fundamental, among them:
Once morphological and physiological characteristics are inherited,
there must be a physical basis for heredity;
2. All hereditary factors must be contained in the gametes, a
since they are the only link between the generations;
3. Gametes cannot be the sole location of hereditary factors, because
some organisms can reproduce asexually and there are
organisms capable of regenerating lost parts;
Hereditary factors may be present and not expressed.
in the short or long term. This suggests that hereditary factors are
relatively stable and enduring even when latent;
5. Hereditary factors can change or completely new factors can emerge.
to be formed, as in the case of the emergence of new variations;
[Link] hereditary factors are present generation after generation
generation, they must replicate themselves;

7. At the time, reputable authorities reported cases where mutilations

seemed to have been inherited and cases where hereditary factors
they seemed to act as infectious agents. Darwin considered these
stories for the formulation of your hypothesis, but nowadays there would be
great doubt regarding the veracity of this information.

When trying to explain all the information available about the

heredity, Darwin made use of, with some refinement,
from the hypothesis of pangenesis formulated by Hippocrates about 2 thousand

years ago. According to Darwin, every part of an organism would produce

gemmules, tiny reproductive units, of specific types. These
gemules would be able to move through the body, so that
all body parts, including eggs and sperm, would contain
gemmules of all types. During development, the gemmules
would unite with each other to produce new cells of the types that the
they had produced; new buds would be produced continuously;
the gametes would generally be active in the offspring, but could remain
sleepers for several generations.

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 AlthoughDarwin'shypothesiswasbasedongemmules,hedidnot
there was no evidence of its existence. The gemmules would be a basis
physics invented to explain the observable phenomenon of heredity.
Inventing an explanation for a phenomenon is a scientific procedure.
legitimate. As we saw, this is what scientists do when they formulate
a hypothesis. The fragility of the pangenesis hypothesis lay in the fact that
she does not simplify heredity — after presenting examples of the
mode of action of heredity, it suggests that inheritance happens
in this way because the gemmules act like this; this is the same as saying
that heredity is synonymous with gemmule. Moreover, in the impossibility
to develop a decisive test for the hypothesis.
Darwin started by trying to explain a great problem and ended up
explaining very little. However, at the time, no one knew any.
another hypothesis better able to explain all existing information
about heredity. Darwin's great contribution was to catalog
and organize a series of information that a comprehensive theory about
Heredity should explain, attribute a physical basis to heredity.
variety, providing other scientists a place to start.
Genetic Science, by its essentially characteristic
experimental, advanced a lot and quickly from the use of
scientific method as a standard procedure for investigation.
Starting from 1900, studies on heredity made great strides.
progress, first trying to explain the simpler cases and only
So, as testable hypotheses were developed, it became
a estudar casos mais complexos, explicando-os e incorporando-os à
genetic theory.

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Basic Genetics | The origins of ideas about heredity

INFORMATION ABOUT THE NEXT CLASS

In the next class, we will see that, in parallel with the studies

they sought general laws for the transmission of inheritance

biological, other researchers were advancing in another
paradigm, the development of cell [Link]
but later, we will also see that it was the integration between

these two ways of seeing nature that allowed the great

THOMAS KUHN
(1923-1996) leap for the understanding of heredity.

Physicist and historian of

science, wrote
The Structure of
Scientific Revolutions,
published in 1962. At the end of this 20th century, it is important to make it clear that
According to Kuhn, everyone that no system will explain the world in all of
paradigm is a
way of seeing seus aspectos e [Link] ajudado na destruição da idéia
the nature. A of an intangible truth may be one of the most valuable
scientific achievement
universally contributions of the scientific methodology.
recognized that,
for some time
time, provides François Jacob (The Logic of Life. A History
problems and solutions of heredity, 1970).
models for
a community of
practitioners of a
science.

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 EXERCISES

1. Identifique no texto abaixo o que podemos considerar como: fato, hipótese,

deductions and how the proposed hypothesis can be tested for falsifiability.

Em meados do século VII, as pessoas acreditavam que o aparecimento de seres

verminous forms would originate from the spontaneous transformation of matter from

decomposing corpses. Francesco Redi, upon seeing flies hovering around

cadavers of various animals, it was supposed that the worm-like beings could be larvae
that emerged from the eggs of these flies. Redi then conducted the following experiment:

put the carcasses of various animals in jars and covered some of them with a
final gaze while leaving others open. In these, where the flies entered, soon
The larvae appeared. In the sealed jars, no worm-like creature appeared.
Observing the development of the larvae, Redi noted the appearance of
identical flies to those that hovered over the corpses. This experiment knocked down

the explanation that worm-like beings arose from spontaneous transformation

of decomposing meat.

Darwin could hypothesize that there were hereditary factors and that they were present.

in at least a large number of cells; they could be transmitted through

two gametes could express themselves or remain dormant in a given
generation, could persist unchanged for generations, could alter under certain
unknown conditions and were able to increase in number.

With the concepts you currently have about the transmission of inheritance
biological, would you be able to identify the genetic processes that explain the
phenomena listed by Darwin. That is:

What is the molecular nature of hereditary factors?

b. In the cells, where are the hereditary factors exactly located?

c. How are these factors transmitted to the next generation?

d. Why a characteristic present in one of the parents does not always express itself
in your descent?

What allows hereditary factors to increase in number, remaining

generation after generation?

f. What causes occasional changes in hereditary factors, resulting in

sudden appearance of new variations?

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Basic Genetics | The origins of ideas about heredity

Try to answer these questions. Don't worry if you can't answer

to some of them. Keep your answers, as they will be used in the future for
to evaluate the evolution of your understanding of the fundamentals of Genetics.

3. Reflect on the text of this first lesson by answering the

questions below:

a. Did the text add any information for you? What?

b. What points did you find most interesting?

c. What points did you consider irrelevant?

Is there any point that was not clear?

Is there any point you would like to elaborate on?

f. Any other comments?

g. In light of your evaluation of this first class, do you intend to take any action?
What attitude improves your learning about the issues raised? Which one?

These are questions you should ask yourself at the end of every class in the course.

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 Cell Division I -
Mitosis and the cell cycle 2
At the end of this class, you should be able to:
Understand the historical events that led to the discovery
of cell division.
Identify the stages of mitosis and relate them to the trans-
mission of hereditary characteristics.
Recognize the stages of the cell cycle.
Basic Genetics | Cell Division I – Mitosis and the Cell Cycle

Surely, you have already studied in the subject Great Themes in

Biology, the works of Robert Hooke (1635-1703), Antony van Leeuwenhoek
Wenhoek (1632-1723) and Theodor Schwann (1810-1882), among others,
and realized that they had a great influence on the formulation of the Theory
Cellular. According to a simplified view of this theory, cells can
to be considered as the basic units of structure and function, that is,
they are the smallest units capable of independent life. In this way,
they are able to use substances obtained from the environment to maintain and produce

the living state. Now, we will see that, despite the cell theory having been for-
born in the first half of the 19th century, it was necessary to have two more
information before the cells could be considered important
for the transmission of hereditary characteristics: (1) the discovery of
that sperm and eggs are cells and (2) the recognition of
that cells only originate from preexisting cells.

THE CYTOLOGICAL NATURE OF THE SPERMATOZOON

When, at the beginning of the 19th century, Schwann and others proposed

that the bodies of organisms would be composed of cells and that the cells
would be characterized by having a matrix surrounded by a membrane,
containing a nucleus inside, it was easy to recognize that the egg
would be a cell. But, in the case of sperm, this association
it wasn't so clear. Although some researchers have proposed the
importance of sperm for fertilization, many others
they were convinced that sperm were parasites. Hence the
term that means "sperm animals." Imagine that, between 1766 and
In 1768, Linnaeus attempted to classify the sperm animals.
It was Leeuwenhoek, in 1667, who first communicated the discovery of

berta de que o líquido seminal possuía criaturas microscópicas e pro-

posed the first hypothesis that sperm would enter the ovum
causing its fertilization (Figure 2.1). But, as we saw, this hypothesis
LAZZAROSPALLANZANI
it was not considered for a long time. More than a century later, in
(1729-1799)
1784,LAZZAROSPALLANZANIconducted a series of experiments to
Italian biologist,
made important to verify the role of semen in reproduction and supported the hypothesis
research in
animal reproduction, Leeuwnhoek. He observed that, when filtering the semen of male frogs,
what contributed
removing the sperm present there, the liquid lost its power
definitely for the
overthrow of the theory of fertilizing.
spontaneous generation of
Aristotle.

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 Figure 2.1: Illustrations of the 'sperm animals' made by Leeuwenhoek.

However, only in 1841 did the idea that spermatozoa were

cells were really accepted by the scientific community, whenLBERT
KÖLLIKER, studying the histology of the testicles, verified that the cells-
the ali present gave rise to the spermatozoa. On the other hand, the RUDOLPHALBERT
VONKÖLLIKER
main evidence that the sperm enters the egg during the
(1817-1905)
fertilization was only given in 1854, by George Newport.
Anatomist and physiologist
Thus, it was established that spermatozoa were cells. gist contributed with
important studies in
that merged with the eggs during sexual reproduction and recognized area of histology.
It was believed that the eggs and sperm should contain the information.
hereditary to be passed on to the next generation.

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Basic Genetics | Cell Division I – Mitosis and the Cell Cycle

The next step was the recognition that every cell comes
from a preexisting cell. After studies conducted with many organisms-
nismos,RU D O L P H V I R C H O W in 1855, proposed: omnis cellula e cellula
(every cell comes from a cell), a phrase that became famous!
Of course, as always happens during development of
new theories, this idea was not immediately accepted by everyone. Many
they continued to believe that organisms could arise spontaneously

R U D O L P H L U D W Islowly.
G But the continuation of research in this area led to the reco-
C A R LV I R C H O W knowledge that the transmission of biological inheritance is related
(1821–1902)
the cell continuity. But what would the process of origin of a
Doctor and sanitation expert
German, devoted himself to cell from another? Would it be possible to identify regularity in this
study of pathology
process?
cell phone. Today is known-
known as "the father of" It was Anton Schneider who made the first description of the changes.
modern pathology
nuclear during the cell division process, in 1873. Observe, in the
Figure 2.2, the illustrations of the images that Schneider saw while analyzing
the initial stages of embryonic development of a flatworm
(Mesostoma sp.).
Note, in the first drawing, the egg surrounded by follicular cells.
and by spiral structures, the spermatozoa. In the other drawings, it is already
possible to identify the process of cell division. Schneider observed the
appearance of rod-shaped structures, which later were
called chromosomes (chromo= colored esomos= bodies) devi-
due to its affinity for dyes. At the end of the division, these structures
would be distributed between the two new cells. Again, it remained
A question: would the rod structures be artifacts of the utilitarian techniques?
covers for fixation and staining of cells? Or are these structures
were they really components of living cells?

Figure 2.2: Illustrations by Schneider (1873) of nuclear changes during the cli-
egg capsule of Mesostoma sp.

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 WALTHERFLEMMING was the one who answered this question when, in
1882, published his observations on cell division in living cells.
of salamander larvae in the book Zellsubstanz, Kern und Zelltheilung.
It was proven that rod-shaped structures were not a
artifact of cytological techniques, for there they were, in the living cells.
Flemming was also able to propose the sequence of events.
related to cell division and describe each of them in detail.
precision that only details of mitosis have been added to yours
description. WALTHER
See in Figure 2.3 the illustrations made by Flemming. The drawings FLEMMING
(1843-1905)
show their attempt to order the events since the beginning of the division,
when the chromosomes begin to become visible, until the formation German anatomist,
of two cells. In addition to the sequence of events, it also calls the one of the first estu-
gods of cytogenetics.
attention, in the larger drawing shown in the second line, to the fact
the chromosomes are duplicated at the beginning of the division.

Figure 2.3: Illustrations by Flemming (1882) showing the nuclear events occurring during mitosis in
living cells of salamander larva.

CED ER J 25
Basic Genetics | Cell Division I - Mitosis and the Cell Cycle

It was Flemming who coined the terms chromatin, mitosis, prophase, metaphase.
the anaphase, which we still use today. He also made the first observations of
mitotic chromosomes in human cells, but the available techniques in
The time did not allow for the identification of the number of chromosomes in our
species. In 1923, Painter, after analyzing human testicular cells, proposed
that our species would have 24 pairs of chromosomes. The correct number of
the chromosomes of the human species (23 pairs) were only established by H. J. Tijo and
A. Levan, in the article "The chromosome numbers of man", published in the volume
42 of the journal Hereditas, in 1956.

UNRAVELING CELL DIVISION

Mitosis is a type of asexual cell division that occurs in

eukaryotes. In this type of division, a cell gives rise to
two daughter cells that have the same number of chromosomes
from the mother cell.

In multicellular organisms, mitosis is responsible for trans-

form the zygote into two cells, then four, eight until an organ
is composed of multiple cells to be formed. Mitosis also
is responsible for the multiplication of unicellular organisms, such as the
protozoa and some fungi.

THE CELL DIVISION CYCLE

The cell division cycle consists of four stages: S (phase
CENTROSSOMO of DNA synthesis), M (cell division phase - Mitosis), G1 and G2 (gap,
Structure or intermediate phases), being a continuous process that takes about
located nearby
to the core of the 10-20 h, depending on the type of cell and stage of development of
animal cells and
vegetables, being the
organism.
primary center Together, the G1, S, and G2 phases constitute the Interphase, the interval between
of organization
two microtubules. mitoses. This is generally the longest phase, occupying about 90% of
In animals, it is
composed of a cycle. The G1 phase begins after mitosis and ends before replication of
pair of centrioles, DNA. The G2 phase starts after DNA replication and precedes cell division.
embedded in a
protein matrix. cell (Figure 2.4). During the G1 and G2 phases, the cell synthesizes proteins
the organelles and monitor the internal and external environments in order to ensure

that the conditions are favorable for replication and cell division. Anaphase
G1 is especially important in this context. Its period may be subject to
large variation, depending on external conditions and signaling
coming from other cells. If the extracellular conditions are unfavourable.
favorable, the cell can interrupt the G1 phase and enter a state
of rest known as G0. In this state, the cell can remain
days, weeks, or even years until the conditions are favorable
26CE OF R J
and she can continue her proliferation.
 Figure 2.4: Cell division cycle.

In the G1 phase, each chromosome in the cell nucleus has a cro-

During the S phase, the DNA of each chromosome replicates. How
as a result of this process, each chromosome has two chromatids
identical (sister chromatids). DNA duplication is fundamental
so that, at the end of mitotic division, the two daughter cells have the
same number of chromosomes as the mother cell. It is also in the S phase that
the duplication of the centrioles in the centrosome begins. Only at the end of the phase

G2, the duplication of the centrioles is complete, but the two pairs are still
remains in a single centrosome.
During Interphase, the chromosomes cannot be seen individually
individually, this is because they are not very compacted and, together,
they take on a knotted appearance. In general, the visualization of each one
The two chromosomes can only be separated during cell division (Figure 2.5).

Figure 2.5: The structure of a

duplicated chromosome to
end of prophase. Each cro-
sister-in-law is formed by
a single molecule of DNA
condensed.

CED ER J 27
Basic Genetics | Cell Division I - Mitosis and the Cell Cycle

CELL DIVISION - PHASES OF MITOSIS

Although mitosis is a continuous process, it is divided into phases.
by cytologists in order to facilitate its description. The phases of mitosis
they are called: prophase, metaphase, anaphase, and telophase. The sequence of
events in each of these phases can be seen in Figure 2.6.
At the beginning of prophase, the duplicated chromosomes, which are found

loose trams contract in a series of helicoidizations, forming

a highly compact structure. This compactness facilitates its moving-
cell nutrition and allows them to be easily visualized
by cytologists. At this stage, the nuclear membrane, referred to as
centromere starts to dissociate. The centromeres divide and each pair
the centrioles migrate to one of the poles of the cell. The nucleolus is no longer

more visible.
At the end of prophase, the chromosomes are already fully condemned.
sados, allowing the visualization of the sister chromatids joined by the region
called centromere or primary constriction. The karyotype, practices-
mind, no longer exists, and each pair of centrioles has already reached a pole of the

cell. From these centrioles, a set of fibers, formed by

polymers of a protein called tubulin project in directions
opposites, forming the achromatic fuses. The kinetochores are formed by the
association of proteins to the centromere and function as sites for
which are connected to the microtubules of the acromatin spindle, whose function is to guide

the movement of chromosomes.

28CE OF R J
Figure 2.6: General scheme of mitosis in animal cells.

CED ER J 29
Basic Genetics | Cell Division I - Mitosis and the Cell Cycle

The stage that is characterized by the alignment of chromosomes in

the equatorial plate of the cell is called metaphase. In stained cells,
we can clearly see the chromosomes attached to the acromatin spindles.
Figure 2.7 shows a schematic diagram of a cell in
metaphase, showing the three sets of microtubules that form
the fibers of the mitotic apparatus. All microtubules have one of their
extremities linked to one of the centrosomes at the poles of the cell. The
aster microtubules project towards the membrane cortex
plasmatic and are attached to it. The chromosomal microtubules remain
connected to the centromeric regions of the chromosomes.
The polar microtubules project toward the center of the cell,
overlapping their distal ends (interaction region).

Figure 2.7: The three sets of microtubules that form the spindle fibers in a
cell in metaphase of mitosis.

The metaphase chromatids are highly helicoid and distinct,

thus facilitating the visualization of the chromosomes. The diagnosis of
disorders caused by structural chromosomal alterations is normal
mind made at this stage.
During anaphase, the sister chromatids of the chromosomes separate.
ram, forming two groups that move oriented by the time zone to the
opposite poles of the cell. This movement is the result of shortening
two chromosomal microtubules. Each chromatid is now considered
an independent chromosome.
In telophase, the chromosomes reach the poles of the spindle.
each pole of the cell. The nuclear envelope and the nucleolus are reformed. The chromosomes

becoming less and less condensed, until they reach their state
the initial compaction. The cell then divides into two through

30CE OF R J
a cytoplasmic division, called cytokinesis. Thus, they are formed-
the two daughter cells and the process of cell division is completed. Each
daughter cell inherits one chromatid from each pair of sister chromatids. From this

In this way, this type of division produces two genetically identical cells.
from a single parent cell.

IS MITOSIS THE ONLY CELL DIVISION PROCESS?

LAR?
As we know, mitosis produces daughter cells with the same
number of chromosomes of the mother cell; the gametes, a bridge between the

generations unite during fertilization and the number of chromosomes

the individuals of a species is constant between generations. Therefore, mitosis
cannot be the only type of cell division, because in that case, the number
the chromosomes should double with each generation.
In the next class, we will see how consistency is maintained in
number of chromosomes between generations, knowing the stages of
another type of cell division, ameiotic, and its importance in the cycle
of the life of eukaryotic organisms.

RESUME

Cell division is just one stage of the cell cycle, which includes three more.
phases: G1 in which the duplication of organelles occurs and precedes replication of
genetic material; S, in which the synthesis of genetic material occurs and the beginning of

duplication of centrioles; and G2, when the cell prepares for division.

Mitosis is a type of asexual cell division that occurs in eukaryotes. In this

type of division, from one cell two daughter cells are formed that
they present the same number of chromosomes as the mother cell. The process begins
with the condensation of the duplicated chromosomes that, in this way, present
two sister chromatids. This stage is called Prophase. The next stage,
called Metaphase, it is characterized by the alignment of the chromosomes on the plate

equatorial of the cell. During Anaphase, the sister chromatids separate and each
a migrates to one pole of the cell. In the last stage, called Telophase, the
chromosomes reach the ends of the spindle at each pole. The cell then
divide into two daughter cells through a cytoplasmic division, called
cytokinesis.

CED ER J 31
Basic Genetics | Cell Division I - Mitosis and the Cell Cycle

EXERCISES

1. Fill in the blanks in sentences 1 to 8 using the term below more

appropriate.

anaphase b) metaphase (c) prophase

d) mitosis (e) telophase (f) interface

1.1 ( ) is a type of nuclear division in which the daughter nuclei retain the same
number of chromosomes of the original nucleus.

The migration of chromosomes to the poles occurs in ( ).

1.3 Chromosomes aligned in the equatorial region of the cell characterize the phase
from the division called ( ).

1.4 ( ) is the first phase of cell division, in which the condensation of

chromosomes, which become evident.

1.5 ( ) is the final phase of cell division, in which the nuclei reorganize.

1.6 DNA replication, that is, chromosome duplication, occurs in ( ).

At the end of ( ), the microtubules of the acromatin spindle are united.

to the cinetocores.

1.8 ( ) is the phase in which the separation of sister chromatids occurs for each

chromosome.

2. What is the structure responsible for the correct distribution of chromosomes?

during cell division? How is it organized?

3. The interphase nucleus is at rest, as the ancients believed.

cytologists? Relate each stage of interphase (G1, S, and G2) to the events that
they occur in the cell nucleus.

4. Why can't mitosis be the only mechanism of cell division?

5. Identify in Flemming's illustrations (Figure 2.3) the schemes that best

Characterize each stage of mitosis. Justify your answer.

32CE DE R J
6. Have you ever heard of a concept map? A conceptual map is a way
schematic representation of knowledge about a given subject or area. The
concepts are indicated in 'boxes' and joined by 'linking words', through
by using arrows, in order to form an expression with meaning, that is,
that reflects valid knowledge in the area.

So, complete the map below using the available terms in such a way that
all concepts should be interconnected through linking words (which can
to be used more than once):

{"se condensam formando":"condense forming","durante a":"during the","produz":"produces"}

["correspond(s) to","they separate at"]

Concepts: prophase, a duplicated chromosome, a DNA molecule,

replication.

!
You can use this type of exercise to test whether you understood how the presented concepts work.
In each class, they are related to each other.

7. Outline all the phases of mitosis of a cell that has 3 pairs of chromosomes.
homologous chromosomes (2n = 6 chromosomes), using the cell below as
model. Take into account the size of the chromosomes and the positioning
two centromeres, so that each chromosome can be identified throughout the
cell division process. Represent only the chromosomes and the fibers of
fuso, don't worry about the other cell structures.

CED ER J 33
 Cell Division II - Meiosis 3
At the end of this lesson, you should be able to:
Understand the historical events that led to
discovery of meiosis.
Identify the stages of meiosis.
Analyze the main life cycles in eukaryotes.
Basic Genetics | Cell Division II - Meiosis

Let's now recall the knowledge that the community

scientific knowledge available, until the end of the 19th century, regarding transmission

of hereditary information:
• The egg and the sperm were recognized as being
germ cells, that is, gametes.
• All somatic cells should contain hereditary information.
necessary for the development of the organism, with the cells
germinative responsible for transmitting this information to the
next generation.
• Gametes, being the only link between generations, should contain
all hereditary information.
• All hereditary information should be contained not only
in germ cells, but also in the cells from which they
they form.
In addition, through the analysis of karyotypes, the scientists of the time
they were convinced that the number of chromosomes of a species
it should be the same for all individuals and in all generations. But,
if they considered mitosis as the only mechanism of cell division,
they should conclude that, when the nuclei of the egg and the sperm
if they merged during fertilization, the number of chromosomes should
double with each generation. One question arose naturally: how to explain
that the quantity of hereditary material remains constant through
the generations? Trying to find an answer to this question,
some hypotheses were raised:
• When the nuclei of the egg and the sperm fuse
However, at the time of the formation of the zygote, the chromosomes also
we would fund each other, avoiding the increase in the number of cro-
we are.
• Half of the chromosomes would be destroyed after the formation of the
zygote, keeping the number of chromosomes constant.
• There would be a mechanism that would reduce the number of chromosomes.
at half during the formation of sperm and eggs in the
gonads and, when fertilization occurred, the number of chromosomes
The zygote would be the same as the previous generation.

And so, how was this issue resolved?

Based on your own observations, and analyzing the ex-peri-
Mentions from other cytologists, August Weismann raised a hypothesis
that seemed to solve the problem of the constancy of the amount of material

36CED ER J
 hereditary through the generations. He believed there should be a
a mechanism that would reduce the amount of hereditary material by half,
during the formation of gametes:
... fertilization consists of the fact that a number
equal legs (chromosomes) of each progenitor to be
placed side by side, and the nucleus of the zygote is with-
placed this way. It doesn't matter, in what it says
regarding this issue, if the loops (chromosomes) of the
two parents merge sooner or later or
if they remain separated. The only essential conclusion
necessary to our hypothesis is that there must be an equal-
complete or approximate date between the quantities
EDOUARD
of hereditary substance provided by each of the VANBENEDEN
progenitors. If so, the germ cells of (1846-1910)
Descendants will contain the germplasms of both. Embryologist
AUGUSTWISE-
united countries, and this implies that such cells can only Belgian cytologist.
MANN(1834-

1914) contains half of the paternal germplasm, as it was

contained in the father's germ cells, and half of the
German biologist,
defended the hypothesis maternal germplasm, as contained in the cells
of existence of germinations of the mother.
germ cells.

(WEISMANN, AUGUST1889. Essays upon heredity and

kindred biological problems. Clarendon Press, Oxford.

At the end of the 19th century, three important researchers,DOUARD

VANBENEDEN,THEODORBOVERIeWIHELMAUGUSTOSKARHERTWIG, encon-
they brought cytological evidence of the mechanism proposed by Weismann.
THEODORBOVERI
(1862-1915)
Analyzing the gametogenesis in cells of female and male Ascaris, a
German cytologist.
intestinal parasite of pigs and humans, these cytologists observed
the occurrence of two different cell divisions during the process
from gametogenesis, resulting in the reduction of the number of chromosomes

half.
This process of cell division that forms the gametes is known as
Cido, nowadays, like meiosis, a word of Greek origin that means
decrease.
The process of meiotic division has begun to arouse great interest
WILHELMAUGUST
in the scientific community. Currently, it can be detailed with a high OSKARHERTWIG
level of precision (Figure 3.3), as you will see throughout this lesson. (1849-1922)
Take the opportunity to compare meiosis with the division process. Cytologist and
embryo-
cell phone that you got to know in the last class, mitosis: check how many German joke.
cells are formed at the end of each process, like chromosomes
they are spatially organized in the dividing cell, what is the relationship between the

duplication of chromosomes and the number of cell divisions, and what the
number of chromosomes found in each daughter cell. CEDERJ 37
Basic Genetics | Cell Division II - Meiosis

! THE MECHANISM OF MEIOSIS

Understand meiosis:
Meiosis is a type of sexual cell division, as it is associated with
To better with-
understand the steps the reproduction in fungi, animals, and plants. Generally, the cell that
from meiosis, read the
text attentively the cell that undergoes meiosis is called a meiocyte. In animals, for example, the
accompanying in
meiócitos are special cells present in the testes and ovaries that will give rise to
Figure 3.4 the pro-
processes that occur origin to the gametes. In most organisms, the meiocytes are cells
during each stage
of meiotic division diploids, that is, each of their chromosomes is represented in
emu maculata animal
diploid(2n=4cro- double dose (homologous chromosomes). In each pair of homologs, one
mosso mos.
one chromosome is of paternal origin and the other is of maternal origin.
At the end of meiosis, four daughter cells will be formed with only
one of the chromosomes from each pair of homologous chromosomes from the mother cell, being

therefore, haploid.
Meiosis is a complex process in which the chromosomal material...
the somatic doubles once and the cell divides twice, reducing
thus the number of chromosomes is halved. The duplication of the material
chromosomal, which corresponds to DNA replication, occurs during
the S phase of the interphase. After replication, each chromosome duplicates-
it comes to have two sister chromatids, as you have already seen in Lesson 2
where the cell division cycle was described. The first meiotic division
(Meiosis I or reduction division) produces two daughter cells with the number
of chromosomes reduced to half, although each chromosome still
contain the sister chromatids. The second meiotic division (Meiosis II
or equational division) is similar to mitosis, with the separation
the sister chromatids of each chromosome. Let's see this process
with more details.
Prophase I is the first stage of Meiosis I, consisting of
five sequential sub-stages: leptotene, zygotene, pachytene, diplotene and
diakinesis. During the first substage (leptonema), the chromosomes
become visible under the optical microscope. The condensation begins in regions
specifics, called chromomers, that have a granular appearance
gradually, the chromosome becomes shorter and thicker.
The terminal regions of the chromosomes, called telomeres, are
linked to the nuclear membrane and this connection seems to play an important role
no matching precise of homologous chromosomes.

38CED ER J
 During the next stage, called zygotene, the chromosomes
homologs pair up, a process called synapse (Figure 3.1).
As the chromosomes have already replicated, each chromosome
it has two chromatids and the pairing of homologs results
in a complex called tetrad (Figure 3.2).

The synaptic complex

Do you know how the homologous chromosomes come together to initiate the process of
pairing? The most accepted hypothesis is that the telomeres of the homologous chromosomes
gaps are connected to adjacent sites on the nuclear membrane and that the synapse starts at these
telomeric regions. For synapsis to occur, the formation of a structure is necessary that
will connect each pair of homologs, called synaptic complex (Figure 3.1). This complex
structure, composed of DNA and proteins, participates in both the synapse and the process of
exchange of genetic material called mutation or crossing over.

Figure 3.1: Synaptic complex. The structure of the synaptic complex is formed between the homologous chromosomes.
during meiosis. The recombination nodules contain the enzymes necessary for genetic recombination.
Note that the representation of the chromosomal fibers includes the two sister chromatids of each homologue.

C E D E R J 39
Basic Genetics | Cellular Division II - Meiosis

(a)
(b)
sister chromatids
of the homolog 1

sister chromatids
to the homolog 2

(d)
(c)

Homologue 1 Homolog 1
Homolog 2
Homolog 2

Figure 3.2: (a) Simplified scheme of the pairing of a pair of chromosomes

we are duplicated homologs, forming the complex known as tetrad.
Each homologous chromosome has two sister chromatids, the result of replication.
of the DNA molecule during interphase, joined by the centromere regions.
Three-dimensional representation that reflects the form more precisely positioning
two homologous chromosomes during pairing. (c) Another way to
represent the same process. In this case, the chromosomes show coloration
different to highlight the fact that one of the homologs has maternal origin
while the other has paternal origin. Note, however, that the sister chromatids
from the same homologues present the same color because they are identical.
Simplest representation to be used in the exercises.

40CED ER J
 In the third sub-stage of prophase I – pachytene – we can already observe
in the optical microscope, the duplicated chromosomes, which continue to
shorten and condense. Permutation, probably, occurs during the
pay attention, but the results of this exchange process only become visible
in the next stage, the diplotene.
During the crossover, the non-sister chromatids of each pair
homologous chromosomes exchange segments of genetic material with each other, orient-

tadas by the synaptic complex, which dissolves at the end of this phase.
The central element of this complex contains DNA loops, which
what are the likely points of recombination. This exchange of material
genetics is important, as it will maintain the pairing of the chromosomes
we are homologous until they bind to the spindle fibers and remain
correctly positioned on the metaphase plate. The exchange is also-
good source of genetic variability in populations.
In the diplotene stage, the homologous chromosomes appear to repel each other.

to others forming structures in the shape of X, called chiasms.

The chiasmata are the contact points between homologous chromosomes.
logos, where the exchange of genetic material occurs. They still maintain
the homologous chromosomes together and provide visual evidence of
that the permutation occurred (Figure 3.3). At the end of the diplotene

the quiasms, apparently, move towards the ends

two chromosomes. Figure 3.3: Schematic of
quasars formed between the
non-sister chromatids of
homologous chromosomes
! paired, during the
prophase of the first division
In many animals, the diplotene stage is very long. In females semiotics.
In humans, for example, this stage begins in the ovary during life.
fetal. About 400,000 immature oocytes reach this stage and, in this
moment, meiosis I stops. The oocytes remain in this stage until
the start of puberty. During the menstrual cycle, one oocyte per month
resumes meiosis in the fallopian tube. Some oocytes may stay permanent
never in the suspended stage of diplotene for several decades. This may have
deep genetic consequences. As the oocyte ages,
increases the difficulty of completing a normal meiosis. The result
are oocytes with abnormal numbers of chromosomes, one of the main
causes of the increase in the incidence of genetic anomalies in offspring of
women with late pregnancy.

During the last stage of prophase I, diakinesis, the nucleolus and

the nuclear membrane disappears and the microtubules that come from the
centrosomes will attach to the kinetochores at the centromeric regions of
chromosomes. In this way, prophase I is completed.
In prophase I, the chromosomes are highly condensed and
paired on the equatorial plate of the cell. The acromantic spindle is
complete.

C E D E R J 41
Basic Genetics | Cell Division II – Meiosis

In meiosis I, homologous chromosomes segregate, migrating

to the poles of the cell. Unlike in mitosis, the sister chromatids
they have not separated yet; therefore, each chromosome remains with
two chromatids. At this stage, the cell begins to divide into two.
Telophase I corresponds to the end of the first meiotic division, the
reduction division. Each of the homologous chromosomes, still duplicated
drop, complete the migration to the poles, forming two new cells
haploids, since each cell formed contains a single set
of chromosomes. In general, at this stage the nuclear membrane is restored, and
Next, cytokinesis occurs.
In most organisms, between the end of meiosis and the beginning of
in meiosis II, an intermediate stage can be identified when the cell
prepares for the second [Link] centrioles duplicate and, normally,
the chromosomes uncoil. In some organisms, however,
the cells skip this step and go directly to the second division
meiosis.
The second division of meiosis, the equational division, is similar to
except the fact that there is only one member of each chromosome.
somic by nucleus. During prophase II, the chromosomes begin to reach
[Link]
that each chromosome is still made up of two sister chromatids.
In metaphase II, the chromosomes align on the equatorial plate.
the separation of the centromeres marks the end of this phase.

During anaphase II, each sister chromatid moves towards one of the
cell poles.
Telophase II marks the end of meiosis, when the nuclear membrane
and the nucleolus reconstitutes itself again. Each nucleus contains a single
chromatid of each chromosome. It follows cytokinesis, division of the cytoplasm.

plasma (see the diagram of the stages of meiosis in Figure 3.4).

A fundamental difference between mitosis and meiosis is that in
In mitosis, there is a duplication of each chromosome for each cell division;
in meiosis there is only one duplication of each chromosome for two
successive divisions. We conclude, then, that mitosis is a mechanism that
maintains the constancy of the chromosome number during cell divisions,
while meiosis reduces this number by half.

42CED ER J
PROPHASE I
Leptotene Zygote Stop it Diplotenon Diacinese
Chromosomes duplicate Homologous chromosomes Homologous chromosomes Homologous chromosomes Chromosomes continue
two become visible. paired geese. totally paired. they start to repel each other. to [Link]
The permutation occurs Chromatids they become and the notebooks disappear.
visible highlighting the Microtubules bind
quasmas. to the cinetócoros in the cen-
trumpeters.

Aster fibers
METAPHASE I
Theassemblyofthespindleiswith-
complete. Each pair of chromosomes-
Polar fibers
we are duplicated homologues
and the paired ones are arranged in the
metaphase plate of the spindle.

Chromosomal fibers

ANAPHASE I

Each pair of chromosomes

duplicate homologs are
separate (segregate), migrating
to one of the poles.

TELOPHASE I

The chromosomes complete

the migration to the poles.

Cell-daughter formed with

homologous theme umbrellas
althoughtheyareduplicated.

Figure 3.4.a: General scheme of meiosis in a diploid animal cell (2n = 4 chromosomes). Note that, at the end
from the first meiotic division, the reduction division, each resulting cell has half the chromosomes of
initial cell (n = 2 chromosomes), although they are duplicated.

C E D E R J 43
Basic Genetics | Cell Division II - Meiosis

Prophase II
Duplicated chromosomes
they condense and limbs-
in nuclear disintegrates.

METAPHASE II

Centromeres linked to
spindle microtubules
through the kinetochores.
Chromosomes align
on the metaphase plate.

ANAPHASE II
Sister chromatids of each chromosome separate (segregate)
and move towards the poles.

TELOPHASE II
The nuclear membrane reforms around the chromosomes and they
they begin to decondense. The nucleolus is reconstituted.

After cytokinesis, four haploid cells are formed.

containing only one of the homologues from each pair.

Figure 3.4.b: General scheme of meiosis in a diploid animal cell (2n = 4 chromosomes).
Note that, since the beginning of the meiotic division, the equational division, each cell has only one cro-
mossomo of each existing pair in the organism (n = 2 chromosomes).

44CED ER J
 It was clear, from the works of van Beneden, Boveri, and others, that
each parent transmits the same number of chromosomes to the zygote.
Furthermore, the chromosomes in the maternal and paternal nuclei appeared to be

identical, that is, each parent contributes one of the chromosomes

of a pair of homologs. These two observations could help explain
what had been believed for some time: that the hereditary contribution
from each parent is approximately the same.
Meanwhile, it was not clear how the characteristics were inherited.
from generation to generation and how they behaved during the formation of
gametes. It wasn't even clear if the chromosomes had anything to do with it
with the transfer of biological inheritance. The connection between chromosomes
and heredity was only proposed in the early years of the twentieth century,
by Sutton, after the rediscovery of Mendel's works.

LIFE CYCLES OF EUKARYOTES

Now that you are familiar with the main stages of meiosis, let's
study the life cycle of some eukaryotic [Link] life cycle of
an organism is the sequence of events that occurs from its origin as
zygote until its death. In eukaryotes, meiosis generates haploid cells
in which the parental genetic material was recombined by segregation
chromosomal and permutation. The fusion of haploid cells produces a
almost infinite variety of new genetic combinations, on which the
evolutionary processes can act. Thus, the life cycles of organisms
present opportunities for the recomposition of genetic material for
to produce new genetic combinations. There are three basic types of cycle
of life: haplobiont haplont, haplobiont diplont and diplobiont. This
classification is based on the ploidy of adult individuals. The terms
haplobiont and diplont refer to the number of types of organisms
regarding ploidy; one type in the case of haplobionts (haploid or diploid)
There are two types in the case of diplobionts (haploid and diploid).

Diplontic haplobiotic cycle

Figure 3.5 summarizes the diplontic haplobiont cycle, the cycle of meiosis.
the animal kingdom, including that of man. The adult body is composed of
diploid cells and meiosis occurs in specialized diploid cells,
the meiocytes, leading to the formation of haploid gametes (meiosis gamé-
The fusion of haploid gametes forms a diploid zygote, which, by
mitosis produces a multicellular organism.

C E D E R J 45
Basic Genetics | Cell Division II – Meiosis

MEIOSIS
GAMETICS

Figure 3.5: Diplontic haplobiont life cycle.

Haplontic haplobiont cycle

Observe in Figure 3.6 the haplobiont haplontic cycle, found

in many fungi and algae. When observing the figure, you must be wondering
tando: how can meiosis occur in a haploid organism? After all,
as we saw, meiosis requires the pairing of two sets of
homologous chromosomes. The answer is that all haploid organisms
those that undergo meiosis go through a temporary diploid stage, in
that will form the meiocytes. In some cases, as happens with the
yeasts, the unicellular haploid individuals fuse to form
a diploid meioocyte, which then undergoes meiosis. In other cases, the
specialized progenitor cells fuse to form
the meiocytes.

MEIOSIS Zigó-
TICA

Figure 3.6: Haplobiont haplont life cycle.

46CED ER J
 Meiosis occurs from the zygote and produces haploid cells that
are called sexual spores (zygotic meiosis). These sexual spores,
in some species, they become unicellular adults. In other species,
each sexual spore develops by mitosis into a haploid individual
multicellular. Thus, you can conclude that, while in a raw-
Zygote formation between two diploid organisms occurs through meiosis for each.

organism, in the crossing between two haploid organisms occurs a

only meiosis in the entire cycle.

Ciclo diplobionte
In an organism with alternation of generations, the life cycle with-
it includes two adult stages: one diploid and the other haploid. One stage
it is usually more prominent than another. It is the life cycle observed
in plants. Observe, in Figure 3.7, that the diploid individual called
sporophyte produces, through meiosis, sexual spores (sporic meiosis). These,
through successive mitoses, it gives rise to a haploid individual, called
of the gametophyte. This individual will produce gametes that, through fertilization,

it originates a diploid zygote. The zygote will multiply through many

mitoses, to form a new sporophyte.

Sporophyte Sporophyte
2n 2n
adult adult

Meiosis Meiosis

n n n n n n n n
Spores Spores
sexual sexual
MEIOSIS SPO- mitoses mitoses
RICA
Gametophyte Gametophyte
an adult an adult

Mitoses Mitoses

mitosis mitosis
Gametes n Gametes n

Zygote 2n Zygote 2n

Figure 3.7: Diplobiont life cycle.

C E D E R J 47
Basic Genetics | Cell Division II - Meiosis

INFORMATION ABOUT THE NEXT CLASS

In the next class, we will study how Mendel's work influenced

in the understanding of the mechanism of transmission of biological inheritance.

SUMMARY

Meiosis is a type of sexual cell division, as it is associated with reproduction in

fungi, animals, and plants. In meiosis, two successive nuclear divisions occur.
In the first of them, the reduction division, the duplicated homologous chromosomes
they pair up and permutation occurs.
Next, each duplicated homolog moves towards a pole of the cell, which,
so it divides into two. Each formed cell has a unique set of
chromosomes, being therefore haploid. In the second division, the equational division,
the sister chromatids, which form the duplicated chromosome, separate. Each
chromatid, then, goes to a pole of the cell that also divides into two. Thus
At the end of the process, the formation of four haploid cells occurs. Neither
meiosis is always related to the formation of gametes (gametic meiosis),
as is the case with organisms that have a diplontic haplobiotic cycle. In the
organisms with haplobiont haplontic cycle, meiosis occurs after formation
from the zygote (zygotic meiosis), and in those with a diplobiontic cycle meiosis is

related to spore formation (sporogenic meiosis).

48CED ER J
 EXERCISES

1. What Weismann imagined was necessary to maintain the constancy of the number
of chromosomes through the generations?

2. Why is prophase I of meiosis considered a highly complex stage?

How the events that occur at this stage can influence transmission of
hereditary characteristics?

3. Complete the diagrams of the two stages of meiosis (I and II) of a cell of
a diploid organism with 2 pairs of chromosomes (2n = 4 chromosomes)
not forgetting to list the main characteristics of each phase. Note that
the chromosomes exhibit distinct coloring to highlight the fact that
one of the homologues has maternal origin while the other has paternal origin
(as in Figure 3.2).

MEIOSIS I

!
Avoid looking at the answer
INTERFACE (G1) no answer key. See the
exercises 3 and 4 how
a challenge to test
your knowledge.
If necessary, ask
helpthetutoranddiscuss
with your colleagues.

PROPHASE I

METAPHASE I

Homologous chromosomes
duplicates and pairs
two are organized on the beach
equatorial.

ANAPHASE I

TELOPHASE I
Two daughter cells are formed containing
only one of the homologs from each pair,
although they are duplicated.

C E D E R J 49
Basic Genetics | Cell Division II - Meiosis

MEIOSIS II

Prophase II
Duplicated chromosomes
they condense.

METAPHASE II

ANAPHASE II

TELOPHASE II

1/2 of the gametes 1/2 of the gametes

4. At the end of meiosis in the previous exercise, only two types of gametes were produced.

formed. However, in the meiosis of another cell of the same individual

other two types of gametes can be formed. Represent, in a way
simplified, the meiosis of this cell, highlighting which phase of meiosis it is that
determine what types of gametes will be formed. Hint: the fact that one of
homologous of each pair have maternal origin while the other has origin
paternal does not imply that the formed gametes necessarily receive both
chromosomes coming from the same progenitor.

5. Now identify the main differences between mitosis and meiosis.

50CED ER J
 6. Considering a human cell, with 46 chromosomes, determine,
justifying your answers, the number of chromatids present (in each
cell) during the following stages of meiotic division:

a) Prophase I

b) Prophase II

c) Telophase I

d) Telophase II

7. Review the life cycle of haploid organisms that undergo meiosis

(Figure 3.6). In the diagram below, the ellipses represent cells of a
haploid fungus that has two chromosomes (n = 2) at each stage of
your life cycle. Now, complete this diagram by placing in each cell
the correct number of chromosomes.

Life cycle of a haploid fungus (n = 2)

Adult (n) Adult (n)

Mitosis Mitosis

Cells (n) Cells (n)

representative representative

Diploid meiocyte
Transitory (2n)
mitosis mitosis

Meiosis

CEDERJ 51
 Mendelism:
the birth of Genetics 4
By the end of this lesson, you should be able to:
• Recognize the historical context in which the discovery took place and
the rediscovery of the fundamental laws of heredity.
Understand the experiments that led Gregor Mendel to
to formulate the Law of Segregation of Factors or First Law of
Mendel.
Understand the basic principles of inheritance transmission.
relating the principles of dominance, segregation of
hereditary factors and random combination of gametes with
the proportions obtained in the genetic crosses involving
a gene.
Basic Genetics | Mendelism: the Birth of Genetics

As you may be noticing, the 19th century marked Biology

due to significant advancements in knowledge in the areas of Cytology and Evolution.

In previous classes, you have already had the opportunity to verify that,
In the 19th century, important studies resulted in the establishment of
Cell Theory is that the publication of On the Origin of Species, by Charles
Darwin, in 1859, revolutionized the thinking about the origin of
diversity of living organisms.
At this time there was also a large number of researchers.
who were engaged in the crossings of plants or animals, usually
called hybridizations, aiming to understand heredity and the bases
of biological evolution. However, there was no knowledge of any
general law that could explain the results obtained. We just need to remember
of Darwin's failure to explain the available information
about heredity through pangeneis (The Variation of Animals
and Plants under domestication, 1868).
The area of study through intersections went through a period
long and unexciting until, in 1900, a modest, underestimated and
forgotten work of a deceased Augustinian monk, has become
known to the scientific community in general. It was about to happen
a paradigm shift. A new Science was emerging, Genetics,
which would soon become a rigorous tool with broad
ability to explain facts and make predictions.
You probably already know who this Augustinian monk is whose work
we are talking.

THE STORY OF MENDEL

Gregor Mendel was born on July 22

1822 in Moravia, then a part of the empire
Habsburg, in Central Europe. His parents were
farmers and rural life taught him to take care of
plants and animals and encouraged their curiosity
about nature.
At 21 years old, Mendel joined the Augustinian monastery of
St. Thomas, in the city of Brünn (now Brno, in the Czech Republic) where
Augustinian monastery could complement their studies.
of St. Thomas, Brno.

54C E D E R J
 After a few years, he was sent to the

University of Vienna, where I frequently attend courses

Physics submits to necessary exams
[Link]
You will succeed in your exams, believe it.
I know that there, Mendel has become aware of the
discussionsaboutbiologicalevolution,athemethat
Since the beginning of the decade of 1850, it was already awakening.
discussionsamongbiologists. Members of the Monastery
Augustinian in the ancient
Even without the credit as a teacher, back to the monastery, Men- Brno between 1861 and 1864.

he devoted himself to teaching and developing his research with

crossbreeding of animals and plants. Mendel was well aware of the work of
Darwin e entusiasmou-se com a questão da evolução. Ele percebeu que,
to understand this phenomenon, it would be necessary to know the fundamentals
of the transmission of inheritance. Mendel began his studies by conducting
crossbreeding with animals (bees and mice), but this type of
the experiment was considered immoral by his superiors, for considering
Remember that Mendel would be playing with sex. Mendel then changed the
focus of their studies on the crossing of plants. Their superiors
they did not realize that plants also had sex.
Mendel conducted experiments with various garden species, but was
with the peas that had the greatest success. The experiments themselves
ditos began in 1856 and ended eight years later, after a
analysis of about 10,000 plants. The results of the research were
presented in two lectures given on February 8 and March 8
from 1865 in Brno Society for the Study of Natural Science and published
Proceedings of this society in the following year under the title: Attempts
About plant hybrids (Experiments in plant hybridization).

!
You can find Mendel's original work translated into English at
address: [Link]

C E D E R J 55
Basic Genetics | Mendelism: the Birth of Genetics

At the time, the importance of Mendel's work was not understood.

The field related to the intersections with plants was full of data that
did not allow general conclusions and the results obtained with the peas
seemed to be just another example of the enormous variation in results
obtained with hybridization. When Mendel wrote to CARLNÄGELI, um
agreatscholarinthearea,sharinghisresults,suggestedthatMendel
repeated his studies with chicory (Hieracium sp). Mendel failed in
C A R LW I L H E L M find the consistent rules for inheritance in this species and itself
VONNÄGELI

(1817-1891) began to believe that their initial results could have application
It was considered restricted. It happens that with Hieracium, Mendel was not conducting the
one two more
crossroads he thought to be. A long time after his death, he discovered-
important
botanists in mid I know that no uniform proportion was to be expected in this kind, because
of the 19th century.
there occurs a type of parthenogenetic development.

Figure 4.1: In species

of the genus Hieracium, the
mother plant can design-
return seeds without being
pollinated. The seeds
they develop directly
cell mind of the bag
embryonic or of the tissues
two adjacent, there are not
meiosis (agemospermia).
In certain species, part
of the seeds unfold-
returns due to aspermia
and another part of eggs
pollinated. This leads to
transmission standards
confused,whereitdoesnotapply
astheassumptionsabout
the laws of Mendel
aregrounded.

Mendel's model was ignored for about 35 years. In

last three decades of the nineteenth century the main scholars of heredity
varieties concentrated primarily on the behavior of the chromosomes.
we are during cell divisions and fertilization. They believed they were
building a physical basis for inheritance, in what they were right.

56C E D E R J
 In 1900, HUGO DEVRIES, in the Netherlands, Carl Correns in Germany-

no, and Erich Von Tschermak, in Austria had the opportunity to

to know Mendel's work. In search of data that supported his
their own theories about heredity, each of them discovered that
the detailed analysis they had done and the essential conclusions to which
haviam chegado já tinham sido apresentadas muito antes por Mendel,
whose work had been forgotten and its meaning not understood.
From then on, Mendel's ideas were increasingly disseminated.
Hugo De Vries
in the scientific community, which began to use them in the formulation of
(1848-1935)
hipóteses, desenvolvendo, como veremos ao longo deste curso, as bases German botanist
of the Science that we now know as Genetics. known for
your studies on
mutations. It was one of
three scientists who,
! regardless,
they rediscovered and
The translation into English of Mendel's letters to Karl Nägeli and the texts they confirmed the laws
of Hugo de Vries, Carl Correns, and Erich Von Tschermak recognizing the value of heredity
Mendel's work as a scientist for the development of theories about presented by
the heredity can be found at the address: [Link] Mendel.
foundations/genetics/classical/holdings/b/[Link].

THE EXPERIMENTS OF MENDEL

In the mid-19th century, the great interest in selection and

hybridization in plants has made available a large number of species
which showed intra-species diversity. Among these was the
pea (Pisum sativum), a species that Mendel chose to conduct
your experiments.
Not that Mendel was particularly interested in peas,
but they seemed to be a good experimental model, presenting
favorable characteristics for the study of character transmission
hereditary. Among these characteristics, we can list:
Worksite where
The wide variety of shapes available; Mendel performed
your experiments.
2. The ease of cultivation;
3. The short generation time;
4. The ease of performing controlled crossings.

C E D E R J 57
Basic Genetics | Mendelism: the Birth of Genetics

The pea flower

In the flowers of the peas (Figure 4.2), the stamens and pistil are covered.
through the petals and, if the flowers are covered to prevent the action of insects, they will
autofecundam. Autopollination is a type of sexual reproduction in which the same
individual provides both gametes, the male and the female, which unite to form
the next generation.

Figure 4.2: Pea flower.

It is also possible to perform cross fertilization by removing the anthers from

a flower before its maturation and later placing the pollen of another plant on
its stigma. Thus, as planned, Mendel could let each lineage...
self-fertilization or perform cross-fertilization between the strains.

Figure 4.3: Cross fertilization.

58C E D E R J
 In principle, Mendel obtained 34 varieties of Pisum sativum.
they presented certain different morphological characteristics and tested them
for two years regarding the consistency of these characteristics through the
generations. Mendel wanted to be sure that the varieties could be
considered pure lines for each of the characteristics.

What did Mendel consider to be a pure lineage?

Pure lineages would be those that by self-fertilization.

they would present all the descendants with the same characteristics
two parents. Let's imagine, for example, a pure lineage of
pea that had the following characteristics: stem length
long, terminal flower position, swollen pod shape and green color. To
if reproducing by self-fertilization, this lineage must show generation
after generation descendants with long stem length, position
from the terminal flower, pod of swollen shape and green color.

a b

Figure 4.4: An example of two varieties of Pisum sativum: on the left, (a), with
the characteristics long stem length, terminal flower position, pod of
inflated shape and green color; on the right, (b), with a short stem length, position
from axial flower, pod with a depressed shape and yellow color.

C E D E R J 59
Basic Genetics | Mendelism: the birth of Genetics

Another investigation done by Mendel before starting his

hybridization experiments were regarding the fertility of the obtained hybrids
in the crossing between these strains. This reduced the number of strains
favorable to 22, as some of the pure strains, when crossed
between them, they did not produce fertile offspring.
Mendel chose seven traits to be studied, each one
presenting two contrasting states of easy classification, such as
show the table below:

Tabela 4.1:Variedades de ervilhas utilizadas por Mendel em seus experimentos.

Characteristics

It was time to start the crossings for real!!! That is, from
of the cross between pure lines that showed characteristics
contrasting, obtain the first generation of hybrids.
The way Mendel analyzed his results was one of the
! fundamental points for the success of your work. Although
The term hybrid, original- other results similar to those obtained by Mendel had already been
mind employed by
Mendel refers to seed Having been described, the rule was to analyze the plan as a whole. As
or individual coming from
at the intersection between two the parent plants differed from each other in several characteristics,
pure line plants
different. Currently, the individuals of the offspring generally presented themselves as
the use of this term
generally refers to the
intermediaries between the parents. Mendel forgot the plant as
individuals coming from a whole and focused on the analysis of the details, on the observation of
inthecrossingofspecies
different. In the text is- one trait at a time. That is, when crossing two lineages
is being employed the
sense that Mendel contrasting in seed color, he wondered only
referred to.
what would be the color of your offspring's seed, not caring,
at first, with the height of the plant or the position of its flowers.
60C E D E R J
THE RESULTS OF MENDEL

For all the analyzed characteristics, the first hybrid generation

(F1) presented plants that displayed the state of the characteristic of a
two parents.
The occurred incident with some of the parental characteristics
What disappeared? Would these characteristics reappear in the next ones?
generations?The answer to this question could be seen from observation.
of the descent of F1 plants obtained through self-fertilization.
The analysis of the characteristics of the F1 offspring by au-
the fertilization presented plants with the most diverse combinations
the characteristics under study. Based on the results obtained, one could
to verify that the character states absent in the F1 generation hybrids
they were not lost; they remained hidden, reappearing in the F2 generation.
Mendel called the state of character that disappeared in the F1 generation of

recessive (due to being in recess), while what remained

in F1 it was called dominant.
To make it clearer, let's imagine an example of
crossing between two pure varieties of Psium sativum to consider
three of the seven characteristics analyzed by Mendel: flower position, color
and the shape of the pod. This crossbreeding is represented in Figure 4.5e,
although hypothetical, presents the same pattern of results obtained by
Mendel in his experiments.

C E D E R J 61
Basic Genetics | Mendelism: the Birth of Genetics

green bean yellow pod

inflated pod depressed pod
terminal flower axillary flower

pollen grain
ovum
zygote

green bean
inflated pod
F1 axillary flower

pollen grains
eggs

zygote

descent of self-fertilization
the F1 plants (Table 4.2)

Figure 4.5: F1 phenotype from the crossing of two pure lines of peas that exhibit
three contrasting characteristics. Subsequently, the self-fertilization of the F1 hybrids, resulting in the second
generation (F2), whose phenotypic proportions are presented in Table 4.2.

62C E D E R J
Table4.2:Descendantsofself-fertilizationofF1plants.

Type Characteristic Quantity

Shape of the pod Green bean color Arrangement of the flower

1 Inflated Green Axillary 2700

2 Inflated Yellow Axillary 900

3 Inflated Green Terminal 900

4 Inflated Yellow Terminal 300

5 Depressed Green Axillary 900

6 Depressed Yellow Axillary 300

7 Depressed Green Terminal 300

8 Depressed Yellow Terminal 100

Total: 6400

For each of the characteristics, what is the dominant form? That is

easy to answer: position of the axillary flower, swollen and green pod, because all of them

the F1 plants exhibited these phenotypes. But, let's go a little

but beyond. Based on the results presented it is possible to reach
some kind of law that governs the inheritance of characteristics
mentioned?
The answer to this question is not easy; many scientists us
past centuries achieved results similar to those presented,
in their experiments on inheritance, and they could not deduce a law
some. The main reason why Mendel was able to determine the
fundamental laws of inheritance was the way he analyzed the
results obtained. He analyzed one characteristic at a time and determined
the proportion with which different types of individuals appeared in the
generation F2. From there, it tried to establish an explanation for the
obtaining these proportions.

C E D E R J 63
Basic Genetics | Mendelism: the Birth of Genetics

In our example, consider one characteristic at a time and check

what proportion of individuals from the F2 generation showed the state of
dominant and recessive traits. Complete the table below:

Proportion between
Total number of individuals with Total number of individuals with
Characteristic individuals with character
dominant character recessive character
dominant and recessive

Shape of the pod

Color of the pod

Position of the flower

Don't remember how to calculate this? See how character is an example.

position of the flower. Of the total of 6400 F2 plants, 4800 are axillary and 1600
They are terminals. That is, for each terminal plant, 3 axillary buds are observed.

In this case, we have the ratio or proportion of 3:1. Your

instead of completing the above table.

64C E D E R J
 The next table presents the results obtained by Mendel.
for each of the seven characters:

Table4.3:ResultsobtainedbyMendelinmonohybridcrosses.

Type of character analyzed Result of self-fertilization

at the intersection between
State of character the F1 plants Reason between
in F1 plants the types F2
pure lineages F2 plants

5.474 smooth
1. texture of the seeds
Lisa 2.96:1
lisa x rugosa
1.850 rough

6.022 yellows
2. color of the seeds
yellow 3.01:1
yellow x green
2.001 greens

705 ashes
3. color of the seed coat
gray 3.15:1
gray x white
224 white

882 inflated
4. texture of the pod
inflated 2.95:1
inflated x depressed
299 depressed

428 greens
5. color of the pod
green 2.82:1
green x yellow
152 yellow

6. position of the flowers

651 axillary
axillary 3.14:1
axillary x terminal
207 terminals

787 long
7. stem length
long 2.84:1
long x short
277 shorts

Didyounoticethatthereishomogeneityintheseresults?Whenconsidering

one characteristic at a time, Mendel verified that, in the F2, the results
they were getting very close to a ratio of 3 plants with the state
of the dominant trait to 1 with the recessive state (proportion)
3:1). In other words, 3/4 (75%) of the F2 plants showed the
dominant state is 1/4 (25%), the recessive state.
Another fact found by Mendel was that reciprocal crossings
they showed similar results. That is, from the intersection between
two pure lineages, one with a dominant character and the other with a character

recessive, regardless of which parental lineage provided the eggs

In the pollen grains, the results obtained in F1 and F2 were similar.

C E D E R J 65
Basic Genetics | Mendelism: the birth of Genetics

Mendel's Hypothesis

Thissimilarityinthebehaviorofsuchdifferentcharacteristics
how the position of the flower and the color of the seeds led Mendel to the conclusion

that there should be some kind of general law governing inheritance of

characters.
NowMendelneededtocomeupwithanexplanationfortheresults
obtained. Invent? Yes, to have a guess about what would be happening.
We can also say in a more scientific way: Mendel should
formulate a hypothesis to explain the observed results.
For Mendel, plants had factors that determined their
hereditary characteristics and were passed from one generation to another
through the gametes. He imagined that a plant would have a swollen pod.
depressed if you received factors of one characteristic or another. Mendel
represented its hypothetical factors by letters, using uppercase form
for the factor that determines the dominant phenotype and the lowercase for the
factor that determines the recessive phenotype.

!
Mendel's hereditary factors are currently called genes.
Genes are segments of DNA molecules that make up chromosomes.
we are. The determining factors of the contrasting states of the same
characteristics are the result of small variations of the same segment
of DNA. But we will see this in detail in later classes.

Considering only one characteristic, the shape of the pod,

Mendel proposed the following model to explain why, starting from
crossing of pure strains, one would obtain in the F2 the ratio of 3:1.
Follow the text, observing the results presented for this
characteristic in Table 4.4.

66C E D E R J
Table 4.4: Let's analyze the shape characteristic of the pod in isolation. The drawings represent the facts.
observed by Mendel and the letters represent the hypothesis formulated by Mendel to explain this data.

Generation P

X
Pure parental lineages
DD dd

GP Gametas Egg 100% D 100% pollen

Generation F1

First hybrid generation

Dd

GF1 gametes Egg 50% D 50% d Pollen 50% D 50% of

Generation F2

DD Dd Dd dd

Descendants of the self-

fertilizationofF1plants DD 2/4 Dd dd

CEDERJ 67
Basic Genetics | Mendelism: the birth of Genetics

Each of the parental lines should possess only one type

of hereditary factor that determined the shape of the pod, and this factor
would be present in your gametes, the link between one generation and another. The

inflated pure lineage, as it only had the inflated factor, would only produce

gametasport inflating factor (D). Similarly, pure alignment

depressed would only produce gametes carrying the depressed factor (d).
The male and female gametes would contribute equally.
in determining the characteristics of the descendants.
3. From the crossing of these two pure lines, there could only be one type of
descent,sincetherewasonlyonetypeofpollenandonetypeofovule.
Adecisivestepintheconstructionofthismodelwastheconclusionthatthe
F1 hybrid seedlings, although presenting an inflated shape, would have,
necessarily,thefactorsDandd.
4. When the F1 plants produced ovules and pollen grains, each
gameta could only present hereditary factors of one type.
That is, the two types of factors present in a hybrid plant
they should separate (segregate) in the formation of gametes, so that
that each gamete carried only one or the other factor, Dou d.
5. The two types of gametes produced by the F1 plants would be in
equal frequency, that is, 50% D and 50% d.
6. Combinations between pollen grains and ovules in the determination of generation

F2wouldbetotallyrandom,resultingin25%DD,50%Dd,and25%
That is, the different pure and hybrid individuals would be distributed
in the ratio of 1 pure dominant: 2 hybrids: 1 pure recessive. How
the D factor is dominant over the d factor, it is observed in generation F2 75%

the plants with swollen pods and 25% with depressed pods.

F1The moon
50%D 50%d
F1Pollen
50%D 25%DD25%Dd Genotypic ratio
expected in F : 2
1DD : 2Dd : 1dd
50%d 25%Dd25%dd

This model is valid for all crossings that involve

just a pair of contrasting states of a characteristic where one
one member of the pair is dominant and the other is recessive.

68C E D E R J
 It should be emphasized that the agreement between the data and the model

is not casual. When we invent a hypothesis, it

it must necessarily explain the data. But, as we saw when studying
the scientific procedure, that does not mean it is true.
The hypothesis can be considered an attempt at an explanation that will be
rejected or not through tests of the deductions made from it.

THE TEST OF MENDEL'S HYPOTHESIS

It was easy to conduct a decisive test. Note that in the F2 generation of

crossroads that we are using as an example (Table 4.4) for each
plant with recessive characteristic (depressed shape), there are three plants with
dominant characteristic (inflated form). This is a fact. However, if
if Mendel's hypothesis were true, the inflated pods should be
of two types, pure (DD) or hybrid (Dd), and in predictable proportions:
among the inflated 1/3 would be DD and 2/3, Dd. Although it was not possible
visually distinguish the DD pods from the Dd, if these plants were
self-fertilized descendants would give the answer.

Table 4.3 presents the total number of inflated pods obtained in F2

in the monohybrid cross conducted by Mendel. If the hypothesis
if Mendel's theory were true, what would the expected outcome be in
descendants of these plants after self-fertilization?
According to the model proposed by Mendel, 2/3 of the 882 plants
the inflated pods present in F2 are hybrids (Dd) and 1/3 are
pure (DD). Thus, after self-fertilization, 294 plants
(1/3 of 882), because they are pure, would produce all offspring
with swollen pod and 588 plants, due to being hybrids,
they would produce from their offspring with swollen pods and with
depressed pod.

Mendel tested his hypothesis by planting the seeds of the

generation F2 and obtained, for the seven characters analyzed, results such as
expected by the above deduction. Therefore, there was no reason for the hypothesis

if Mendel were rejected and, in a synthetic manner, the Law of Segregation of

Factors or Mendel's First Law can be expressed as follows:
The basic principle of biological inheritance establishes that the

hereditary characteristics are determined by factors that

occur in pairs. In the formation of gametes, the factors are members
from each pair they segregate, that is, they separate in such a way that each

gameta only receives one member from each pair of factors, being,

therefore, always pure.

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Basic Genetics | Mendelism: the Birth of Genetics

INFORMATION ABOUT THE NEXT CLASS

In the next class, we will continue the analysis of Mendel's work.

investigating the pattern of inheritance transmission of two or more traits
together.

SUMMARY

In 1865, Mendel presented the results of his research on hybridization in

Pisum sativum two lectures held at the Brünn Society for the Study of
Natural Science. Although these lectures have been published in the Proceedings
of this society the following year with the title: Experiments on Plant Hybrids
(Experiments in plant hybridization), the importance of Mendel's work
was not immediately understood by the scientific community and was forgotten
until, in 1900, it was rediscovered by Hugo de Vries, Carl Correns, and Erich Von
Tschermak. From then on, Mendel's ideas were increasingly disseminated.
in the scientific community, which began to use them in the formulation of hypotheses,
developing, as we will see throughout this course, the foundations of the Science that today

we know as Genetics.

Mendel observed that:

1. In the crossing of two pure varieties that differ from each other regarding a
certain hereditary character, the trait that does not appear in the F1 generation
it is not lost, but becomes concealed, reappearing in F2.
2. In F2, the ratio between the number of individuals exhibiting the form
the dominant form of a characteristic and those that present the recessive form is 3:1.

3. Reciprocal crossings yield similar results.

Mendel concluded that:

1. The male and female gametes contribute equally in
determination of the characteristics of the descendants.
2. Hereditary characteristics are determined by factors that are passed down from
from generation to generation through gametes.

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3. The F2 generation of a cross where the parental types differ in
a characteristic is made up of three types of individuals, in the ratio of 1
pure dominant: 2 hybrids: 1 pure recessive. This proportion is the result of,
in the F1 generation, a hybrid for a certain pair of factors to form only
pure gametes and these gametes randomly unite to give rise to the generation
next.

Based on these conclusions, Mendel formulated his first law, also known
as the Law of Segregation of Factors or the Law of Pure Gametes, which can
is expressed as follows: "The basic principle of biological inheritance establishes
that hereditary characteristics are determined by factors that occur to
In the formation of gametes, the factors members of each pair segregate,
that is, they separate in such a way that each gamete receives only one member of each pair

of factors, being therefore always pure.

EXERCISES

1. Fill in the blanks using the most appropriate term below.

dominant phenotype
(b) genotype monohybrid
segregation (g) recessive
generation F1 generation F2

Mendel called it ( the state of the characteristic that appeared in all the
plants of the first hybrid generation.

The state of the characteristic that did not appear in the hybrid individuals was called
by Mendel of ( ).

The first hybrid generation, that is, the one resulting from the crossing between
individuals of different varieties are called ).
The descent resulting from the self-fertilization of the first hybrid generation is

call of ( ).

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Basic Genetics | Mendelism: the Birth of Genetics

The term ) is used to designate the characteristics presented by a

individual, whether they are morphological, physiological, or behavioral.

The term It refers to the genetic constitution of the individual, that is, to the factors

hereditary, or genes, that he possesses.

A cross ( ) involves individuals that differ only in one trait,

with two contrasting states.

The purity of gametes is the result of ) of the factors of each pair in the formation
two gametes.

2. What were the reasons that led Mendel to choose the pea as material for
your experiments?

3. How Mendel's analysis differed from that of his predecessors who worked
with plant hybridization?

4. What do you understand by self-fertilization and cross-fertilization?

5. Based on Mendel's hypotheses and observations, outline the results.

expected in the following crossings:

a. pea with gray seed coating (dominant) with pea with

white seed coating.
b.F1 in the crossing (a) with each other.

c.F1 from the cross (a) with the pea with white seed coat.

6. If you have a Pisum sativum with swollen pod type (characteristic

dominant), what kind of test could be done to determine if it is pure
Are you hybrid according to Mendel's criteria?

7. Coleus blumei is a species of plant widely used in garden ornamentation.

which can present its leaves with slightly wavy edges (crenate shape)
or deeply cut (lobed shape). When making a cross between
a plant of this species showing crenate leaves with another showing
lobed leaves, a producer obtained only lobed leaves in the offspring. With
based on these results, the producer concluded that the factors that condition the
crested forms are not transmitted to the offspring in this type of crossbreeding.

Do you agree with the conclusion drawn by this producer? If you do not agree,
propose a hypothesis to explain the obtained result. How could you
test your hypothesis experimentally?

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8. The French biologist Cuenot, in the early 20th century, crossed wild mice.
of gray color with white (albino) mice. In the first generation all
the individuals had gray color. The crossing of these last individuals among themselves
produced a generation F2consisting of 198 gray mice and 72 white mice.

Propose a hypothesis to explain these results. Based on your hypothesis,

make a crossing diagram and compare the observed results with the
expected according to the diagram.

One of the different types of albinism that occur in the human species is
determined by a recessive factor.

a. Of the marriage between a woman carrying the gene for albinism (Aa) and
an albino man, what is the expected proportion of albino children?

b. From the marriage between two carriers (Aa), what is the expected proportion of children?

albinos?

In some breeds of cattle, the absence of horns is conditioned.

by a dominant factor (C). A hornless bull was crossed with three cows. In the
crossbreeding with cow I, horned, a calf without was produced
horns. In the crossing with cow II, carrier of horns, a was produced a
calf with horns. In the crossbreeding with cow III, hornless, a was produced a
calf with horns.

a. Propose a hypothesis to explain these results.

Based on your hypothesis, create a cross diagram and compare them.

observed results compared to the expected ones according to the diagram.

C E D E R J 73
 The work of Mendel:
unraveling the Second Law 5
By the end of this lesson, you should be able to:
Understand the model proposed by Mendel
to explain the results obtained in the
crossings involving two characteristics
(hybrid crossing).
State Mendel's Second Law, the law of
segregation or independent association.

Prerequisites
You will need to review the
concepts of the theory of
probabilities: rules of the
addition and multiplication
presented in the classes of
Biostatistics. It's the First
Mendel's law.
Basic Genetics | Mendel's work: unraveling the Second Law

In the last class, we saw how Mendel explained the pattern

of inheritance transmission in pea considering some of the
Characteristics of the species Pisum sativum in isolation.
Mendel postulated that hereditary characteristics are
terminated by factors that occur in pairs. In the characteristics
analyzed by Mendel, in each pair of factors, one member of the pair
is dominant and the other, recessive. The factors members of each pair are
separate (segregate) in the formation of gametes, with each gamete
receives only one factor from each pair. The random combination of gametes
during fertilization produces, then, three types of descendants: 1/4
with the two dominant factors (homozygous dominant); 2/4 with
a dominant factor and a recessive one (heterozygous) and 1/4 with both
recessive factors (homozygous recessive). Once the homozygous
dominants and the heterozygotes are indistinguishable from each other, the proportion

the expected phenotypic model is of 3 individuals with phenotype

dominant for 1 individual with a recessive phenotype.

!
We call monohybrid crossings those in which only one
the contrasting characteristics between the two parental lineages are
analyzed. In the hybrid crosses, the analysis includes two characteristics
contrasting between the parental lineages.

ANALYZING TWO CHARACTERISTICS

IN CONJUNCTION - HYBRID CROSSINGS

What if we analyzed two or more characteristics simultaneously?

whatwouldbethetransmissionpatternofthecharacteristicsofoneinrelationto
Another? Would these characteristics be inherited according to a defined pattern?
Mendel must have asked a question similar to this when
It decided to consider two characteristics in its analyses at the same time.

time. To simplify understanding, let’s take as an example the

crossbreeding between two pure lines that exhibited the traits
color and texture of contrasting seeds. In other words, one of the lineages
The parents had smooth yellow seeds and the other had wrinkled green seeds. The F1

this crossing produced all smooth yellow seeds, that is,

presented the state of dominant character for the two characteristics
in question. The self-fertilization of the F1 plants provided in the F2 the
the following types of seeds:

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 Phenotype Number of seeds Observed proportions

Yellow-smooth 315 9.8

Solid Green 108 3.4

Rugose yellow 101 3.2

Wrinkled green 32 1

The result is the proportion of 9.8(315/32) : 3.4(108/32) : 3.2(101/

These proportions represent the actual data obtained.
in this sample with a total of 556 plants, but Mendel proposed that
the theoretical ratios should be 9:3:3:1. You may have already seen it in
bioinformatics course that, when we work with samples, we can
obtain deviations from the expected theoretical values. We will revisit this in classes

future. For now, let's try to understand why Mendel considered

that the theoretical ratio of the F2 should be 9:3:3:1. Or, in other words,
that 9/16 of F2 show both dominant states, 3/16 show
one dominant state and the other recessive, 3/16 present the other
dominant is the first recessive and 1/16 shows both recessive.
First of all, because values close to these proportions
were obtained for all experiments when he considered two
simultaneous characteristics. This regularity indicated that it should
there is some fundamental principle responsible for it. Secondly, because
he was able to predict that these proportions would be obtained from the
3:1 ratios of monohybrid crosses. Do you want to know how?
Let's find out...
From the hybrid cross we took as an example
(yellow smooth seed pea x green wrinkled seed pea)
to analyze the proportions of F2 considering a characteristic
for once. For the seed color we will check that 416 are yellow and
140 are green. Which gives a ratio of 2.9 : 1, a small deviation.
of the theoretical ratio 3:1. Now calculate the ratio of F2 to the other
characteristic, seed texture.

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Basic Genetics | Mendel's work: unveiling the Second Law

What did you observe? That's right, the ratio 3:1 also
it is maintained.

So the ratio 9:3:3:1 must be a combination of the

proportions 3:1 of each of the characteristics. Mendel, who was a physicist
and knew math well, so he realized that he could apply the laws of
probability to explain your results.
Shall we try to solve this issue? First, let's analyze.
the characteristics separately. With your knowledge of prob
abilities (if necessary, review the rules of multiplication and addition of
probabilities in the course of Biostatistics), answer about F2 of
crossing of the above example:
1. How often should individuals with the
dominant yellow characteristic?
416/140 => ratio 3 yellow : 1 green => frequency of
The sample is yellow.
2. How often should individuals with the
recessive green characteristic?
3. How often should individuals with the
dominant characteristic smooth?
4. How often should individuals with the
recessive wrinkled trait?

By now you should have no doubts. The answers would be,

respectively, 3/4; 1/4; 3/4 and 1/4. Now let's consider the two
simultaneously characteristics and, as Mendel soon realized, we will
Consider the transmission of characteristic when an event occurs
regardless of the transmission of the characteristic texture of the seed.

!
What is the probability of getting heads twice when tossing a coin?
two coins?
The simultaneous launches of two coins constitute
independent events. The probability of two or more events
independent events occurring together is the product of the probabilities with
which occur separately. Thus, the probability of obtaining two
the times the face occurs in two launches is equal to 1/2 x 1/2, or 1/4. In other words,
we expect to get two heads once every four times we throw
two coins simultaneously.

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 5. How often should individuals with the
dominant characteristics yellow color and smooth texture?
The answer will be the product of the independent probabilities.
The probability of being yellow = P(yellow) = 3/4 and the
probability of being smooth = P(smooth) = 3/4, the probability of being
yellow and smooth = P(yellow and smooth) will be:

P(yellow and smooth) = P(yellow) x P(smooth) = 3/4 x 3/4 = 9/16.

Oops!!! This number is not unfamiliar to us. So, if the transmission
if the seed color characteristic is an independent event
from the transmission of the characteristic texture of the seed, in a

I would expect a sample of the F2 for every sixteen plants.

new ones presented yellow and smooth seeds.

You answer the other questions.

6. How often should individuals with the
dominant characteristic is yellow color and recessive is texture
rugose?
7. How often should individuals appear with the
Is the green color a recessive characteristic and the smooth texture a dominant one?

8. How often should individuals with the

recessive traits green color and rough texture?

You solved the riddle!!! If the transmission of the two characteristics

for independent events, from the product of the probabilities
From each of them we can explain the phenotypic proportions.
9:3:3:1 of F2.
When considering, based on the crossings you made, two
the seven characteristics simultaneously, Mendel obtained results
similar to the one described above for the color and shape of the seeds. Although

the proportions obtained experimentally could differ slightly

from the ratio 9:3:3:1, Mendel considered that this would be the result of
random deviations from the theoretical expected and that there should be a principle

fundamental responsible for the observed pattern.

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Basic Genetics | Mendel's Work: Unraveling the Second Law

Mendel's hypothesis for the dihybrid cross

To explain his results, Mendel proposed that the factors for

two or more characteristics should segregate independently
in the formation of gametes of hybrid plants — law of segregation
independent (also known as Mendel's Second Law or law
from the independent association).

That is, each gamete should receive only one factor for each
Characteristic: V ou, for the factors that condition the color of the seed
yellow or green, and R our, for the factors that condition its texture
smooth or wrinkled. The factors for the two characteristics would combine at
A S S O C I AT I O N in the formation of gametesINDEPENDENT ASSOCIATION OF FACTORS).Na
INDEPENDENT
hybrid plant (F1) of our example, a gamete that had received the
TWOFACTORS
dominant factor for one of the characteristics (V) could receive both the
In the F1 plants
from an intersection dominant factor (R) as well as the recessive (r) of the other; in the same way,
dihybrid for color and
shape of the seed, agametethathadreceivedtherecessivefactor(v)couldreceiveboththe
segregation
independent of the
dominant factor (R) as well as the recessive (r). A dihybrid plant would form,
factors of each one therefore, four types of gametes: VR, Vr, vR, vr (Figure 5.1).
the characteristics
produces four types
of the gametes in
equal proportions.

Factor V segregates from factor v

Figure 5.1: Association

regardless of the factors
in the formation of gametes
ofadihybridindividual.

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 During fertilization, the gametes would unite randomly, that is,
each type of pollen would have an equal probability of joining any type
of the ovum (Figure 5.2).

Segregation of Rr factors and Vv factors

in the formation of pollen grains

Type of frequency of the genotype of pollen grains

Segregation of the factors

Rr is two factors Vv
two eggs

Type of frequency of the

genotypes of the eggs

Figure 5.2: Representation of Mendel's hypothesis to explain

the results of the hybrid cross for color and shape of the
seed. Each individual of F1 (VvRr) produces gametes as
described in Figure 5.1. The combination of hereditary factors
in F2 will be determined by the random combination of the four
gametes produced in equal frequency. Knowing these
combinations and knowing that factors are dominant
for each characteristic, the phenotypic proportions can
be determined.

But note one very important thing. For the classes

observed phenotypes in F2 were in the ratio of 9:3:3:1, there is
some other conditions that should be met. From the
hybrid cross scheme of Figure 5.2, try to identify
these conditions. See? So, let's list them:

The four types of gametes formed by the dihybrid plant

they should appear with equal frequency, that is, 25% (or 1/4)
each one.
2. For each of the analyzed characteristics, there must be dominion-
complete dependence of one of the factors on the other.
The factors that determine one of the characteristics should not
to influence the determination of the other characteristic.

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Basic Genetics | Mendel's Work: Unraveling the Second Law

If any of the listed conditions are not met, the

phenotypic proportions in the F2 will be different.
Let's analyze the condition that each type of gamete is
formed with equal frequency, that is, 1/4 RV; 1/4 Rv; 1/4 rV; 1/4 rv.
In Figure 5.2, observe the frequency of each gamete and the classes.
resulting from the random crossing between them. For example, 1/4 of the
Eggs would be RV and 1/4 of the pollen grains would be rV. Therefore, in 1/4 x

1/4, or 1/16, of the time a pollen grain rV would fertilize an ovule RV

forming a plant that would have the Rr factors for seed shape
and VV for the seed color and would have the phenotype smooth yellow seeds.
Note that 9 out of 16 combinations of pollen grains and ovules would produce
smooth yellow seeds in F2. The same reasoning can be applied to
the other phenotypic classes.
In summary, the condition that gametes are formed in the
same frequencies (1/4 of each type) are essential to explain the
observed results in the F2 of the dihybrid crosses. If we violate
this or any of the other conditions mentioned, we will see that the proportion-

Phenotypic ratio in F2 will no longer be 9:3:3:1.

THE HYPOTHESIS TEST OF MENDEL FOR THE MODEL

OF HYBRID CROSSBREEDING

After proposing a model to explain the results obtained in

with hybrid crossings, Mendel was able to make predictions and test them. It is
I need to make it clear that the only data available to Mendel was
the phenotypes of plants and their frequencies in generations. Everything else makes

part of the model created by him to explain these results.

Reviewing Figure 5.2, it is possible to identify that, according to the hypothesis

Mendel stated that the smooth and green seeds of the F2 should be of two types,
given that, 1/3 of them would be of type vvRR and 2/3 would be of type vvRr. A
From there, Mendel could test his hypothesis, as he could predict that,
if your hypothesis were correct, by leaving the plants with seeds
the green peas of F2 self-fertilizing, 1/3 of them should show
descendants with 100% smooth and green seeds and 2/3 of them should
present offspring with 3/4 of the smooth green seeds and 1/4 of the
rough green seeds. Mendel made similar predictions for all
the phenotypes obtained in F2 and tested them, obtaining the expected results
for your hypothesis.

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Table 5.1: Mendel's hypothesis test for the dihybrid cross.

Types of plants Expected result for

with seeds the self-fertilization of Expected result Result obtained after the
green-plain from F2, smooth green plants of F2, aposeautofecundação self-fertilization of 102
according to the hyp- according to the hypothesis of of 102 plants of the F2 plants of F2
Mendel's thesis Mendel

100% vvRR 100% plain green 1/3of102=34plants 35 plants presented

1/3 vvRR with descent F3 with all decency-
green-smooth green-smooth residence

1/4 vvRR 75% green-smooth

2/4 vvRr
67 plants showed
2/3 of 102 = 68 plants
descendants with, approx-
with descent from
2/3 vvRr maturely, 3 seeds
3 green-lisa: 1 green-
green-stripes: 1 green-
rugosa
1/4 vvrr 25% rough green rugosa.

One objective of all hypotheses and theories in science is their

power of prediction. Mendelian hypotheses allowed for the formulation
of such a specific model that, from it, deductions could be
made and tested through observations and experiments. In 1865,
no field of Experimental Biology had reached an equivalent
level of development. Mendel's experiments with crosses
of varieties of peas and their remarkable analysis of the results led
to important conclusions, initially valid only for peas and
subsequently demonstrated as universal principles of Genetics.

INFORMATION FOR NEXT CLASS

In the next class, we will see how the first ideas about the factors emerged.
heredity would be located on the chromosomes.

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Basic Genetics | Mendel's Work: Unraveling the Second Law

RESUME

Through studies conducted on peas (Pisum sativum), Mendel recognized

that the transmission of inheritance followed defined rules and proposed a model

explanatory for these rules. The passing of time showed that the conclusions
Mendel's experiments with peas were general and applicable to other species. The
the fundamentals of the proposed model are:

1. Heredity is conditioned by factors transmitted through

gametes, from generation to generation. For each characteristic there may be factors

various, responsible for determining their different states.

2. The conditioning factors of the contrasting states of the same characteristic

they can present a dominance-recessiveness relationship with each other, and only
one of them (dominant) manifests in the hybrids.

3. When two varieties of plants are crossed with each other, there is no mixing of the
factors of heredity that determine the contrasting states of their
characteristics. The hybrid resulting from these crosses is identical in appearance,
to pure dominant parent.

4. The two types of hereditary factors present in the hybrid (A and a) separate.
in the formation of gametes and combine randomly during fertilization,
resulting in a phenotypic ratio of 3:1. This ratio can only occur if
each gamete receives a type of hereditary factor, Aoua.

5. Each pair of factors in a dihybrid plant, such as AaBb, behaves in a way

independent of the other pair. Thus, the members of the pair segregate.
be independent of the members of the parBb, producing four types of
gametes in equal frequencies: 1/4AB, 1/4Ab, 1/4aB, 1/4ab. The gametes thus
formed combine randomly in fertilization, resulting in four
types of descendants in the ratio 9:3:3:1.

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 EXERCISES

Use the alternatives below to answer questions 1 and 2.

association

dominance

independent segregation

segregation

The purity of the gametes is the result of the ( ) of the factors of each pair in the formation.

two gametes.

The four types of gametes that a dihybrid forms is a consequence of ( ) the

factors of the two pairs.

3. How can the 9:3:3:1 ratio typical of a dihybrid cross be derived?

based on the proportion 3:1, typical of a monohybrid cross?

4. Answer the following questions:

a. What are the necessary conditions for the Mendelian model to be valid
Could they be considered facts?
b. What is the basic difference between the 1st and 2nd Laws of Mendel?

5. Based on Mendel's hypotheses and observations, outline the results.

expected in the following crosses in peas:
a. pure strain of tall pea and swollen pod × pure strain of pea
dwarf and depressed pod.
b. F1 in the cross (a) among themselves.

c. F1 from the cross (a) × original dwarf pea line and depressed pod.

6. Assuming independent segregation, how many types of gametes are there for each
Does the individual below produce?

I AaBbCCdd
II AaBbCc
III AabbCcDDEe

Use the alternatives below to complete sentences 7 to 11.

(a) 1:1 (d) 1:1:1:1

1:2:1 (e) 9:3:3:1
(c) 3:1

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Basic Genetics | Mendel's Work: Unraveling the Second Law

7. In the crossings involving only a pair of contrasting characters,

Mendel obtained individuals with dominant and recessive traits in the F2 generation.
in the proportion of ( ).

8. When Mendel followed the inheritance of two traits, that is, in crosses
hybrids, found in generation F2 individuals with both dominant states
for the two characteristics analyzed, one dominant and the other recessive, with
one is recessive and the other is dominant and with both being recessive, respectively,
in the proportion of ( ).

9. The proportion of ( ) in generation F2 would correspond, according to the model of

monohybridism, to the genotypes of the pure dominant individuals, hybrids and

recessive, respectively.

10. A heterozygous organism for a pair of factors will form

gametes in the proportion of ( ).

11. A double-heterozygous organism regarding two pairs of factors with

independent segregation will form gametes in the proportion of ( ).

12. In the crossing between a pure line of yellow, smooth seed and covering
gray with another of green-wrinkled seed and white wrapping, Mendel obtained in
F1 all the smooth yellow seeds with a gray coating.

a. According to the laws of segregation and independent assortment, how many

What types of gametes should be produced by the tri-hybrid F1 plants?

b. How many combinations of gametes can be produced from the

self-fertilization of F1 plants?

c. Figure 5.3 presents the 'branch method'. This method can be used
to calculate the expected frequencies of each of the phenotypic classes
From F2. Complete Figure 5.3, estimating the expected phenotypic proportions.
in the F2 of the trihybrid cross.

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Phenotypic reasons determined by each pair of factors

Phenotypes
Seeds Seeds seed coverings Phenotypic ratio
lisa x rugosa yellow x green gray x white expected in F2

3/4

Gray

3/4

Yellow
1/4

3/4

White

Lisa

3/4Gray

1/4

Green

1/4

White

3/4 Gray

3/4

Yellow
1/4

White

1/4 Wrinkled
3/4Gray

1/4

Green

Figure 5.3: Predicting the proportions

phenotypic traits in the offspring of a cross-
hybrid breeding through the method
of branches.
1/4 White

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Basic Genetics | Mendel's work: uncovering the Second Law

APPENDIX
NULL HYPOTHESIS
(H 0 )
It is a hypothesis HYPOTHESIS TEST: THE CHI-SQUARE DISTRIBUTION
statistics to be tes-
ta-da, being able to be
rejected or not of
In experimental crosses, we often observe
agreement with the pro- phenotypic proportions that show deviations from the expected values of
probability that
the mathematical deviations according to our hypothesis. Statistically, we can test if these
ticks between the resul-
deviations are significant or not. In other words, we can test if the results
observed data
no experiment observed in an experiment are in accordance with a specific
and the results
expected for this
hypothesis.
hypothesis must be In the case of frequency analysis, the chi-square test (χ ) is a 2
by chance.
It is called a hypothesis of the most used. Our goal in this appendix is to show, in the way
null, as it is about as direct as possible, the application of this test in genetic experiments.
from a statement to
regarding the absence More rigorous approaches can be obtained in the teaching material that
of differences (dife-
null reference). Thus,
you received in the course of Elements of Mathematics and Statistics, or in
if at the end of the test specialized books like the Practical Course in Biostatistics; see the
we could not reject
to take the null hypothesis, bibliographic references.
we will have a case
The test compares an observed frequency distribution with
in what the data
observed are from a distribution of theoretical frequencies. In what way? When
agreement with the espe-
broken by this hyp- we calculate the value of theχ , the
2
deviations that occurred in relation to the values-
thesis, that is, the pro-
the expected results are converted into the probability of obtaining a deviation
possibility that
the deviations have of this magnitude or greater at random, taking into account the size of
happened by chance
it's high (usually sample and the number of classes (the degrees of freedom). It became complicated.
greater than 5%)
while, if Fell? Let's analyze the purpose of this test during its application.
to reject the hy- Refer to Table 5.2, where the results are presented.
zero thesis, we will have
a case in which the of two crossings. The first crossing (I) was carried out between a
observed data
they do not agree variety of pea with yellow and smooth seeds, double-heterozygous
as expected by
RrVv, a variety with green and wrinkled seeds, double homozygous-
this hypothesis, this
is the probability recessive trait rrvv. The number of individuals observed in each one of the
of what the deviations
have occurred to phenotypic classes in the offspring of this cross are in the first column.
Is it significant?
again small
Columns two and three present, respectively, the proportion and the
(usually smaller expected number of individuals, if the genes that condition the two
than 5%). In this
case, therefore, must characteristics segregate independently.
to have a cause
that explains the dis- The second cross (II) was carried out between a variety of
found vios, and scented pea, double heterozygous for the flower color traits
a new hypothesis
must be formulated, and the shape of the pollen is a variety of double homozygous recessive, seized-
the alternative hypothesis
sitting the color of the red flower and the shape of the round pollen. The segregation
go (HA).
independence was also used as a null hypothesis for the calculation of
expected proportions in this crossing.

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 Observed Proportion Expected
Phenotypic classes (O - E)2 (O - E)2/ E
(O) expected (E)

yellow-smooth 252 1/4 252 (252-252)2 0/250 = 0.000

green–wrinkled 248 1/4 252 (248-252)2 16/250 = 0.064

I yellow–rough 250 1/4 252 (250-252)2 4/250 = 0,016

green smooth 258 1/4 252 (258-252)2 36/250 = 0.144

TOTAL (Σ) 1008 1 1008 – χ 20.224

purple-long 567 1/4 225 (567-225) 2 116964/225 = 519.84

purple-round 46 1/4 225 (46-225)2 32041/225 = 142.40

II
long-red 48 1/4 225 (48-225)2 31329/225 = 139.24

red-round 142 1/4 225 (142-225)2 6889/225 = 30.62

TOTAL (Σ) 900 1 900 – χ 2= 832,100

Table 5.2: Value of chi-square (χ ) calculated 2

for (I) the result of a crossing between varieties
de ervilha que diferem quanto à cor e quanto à forma das sementes; e (II) resultado de um cruzamento
among varieties of sweet pea that differ in flower color and pollen size.
Observed (O) is the number of individuals observed for each phenotypic class, Expected proportion is
calculated by the null hypothesis to be tested (law of independent segregation), Expected (E) is the number
of individuals expected by the null hypothesis (in the same total as the number of observed individuals).

Note that the expected number of individuals is calculated at

relation to the total number of individuals observed. Just multiply the
total number of individuals, observed by the expected ratio in each class
phenotypic. In the first cross, for example, the total observed is
1008 individuals and the expected proportion in each phenotypic class is 1/4.
Logo, the expected number of individuals (E) in each phenotypic class
1008 x 1/4 = 252.
The value of theχ is2 obtained through the sum of the squares of the dis-
variance between the observed number of individuals (O) and the expected number

(E) for the hypothesis to be tested (theNULL HYPOTHESIS), divided by the number
expected

χ 2= Σ [(O – E)2/ E]

Attention: the test ofχ it must

2
always be done with absolute values,
never with proportions. The use of proportions eliminates information
fundamental for the statistical test, which is the sample size.

C E D E R J 89
Basic Genetics | Mendel's Work: Unraveling the Second Law

With the values of theχ calculated

2
for the results of each crude-
zamento ( χ calculated),
2
we can test if each result is in accordance
with the law of independent segregation (our null hypothesis - H 0through
from the comparison of these values with the critical value ofχ (χ critic).
2 2
The
χ 2the critic determines from what value the probability of deviations
happening at random (P) is less than theSIGNIFICANCE LEVEL(α) do
test, that is, from what value can we say that the difference between
the observed and the expected is too great to be solely due to
at random. In practice, there are two possible outcomes (usually
we useα = 0.05):
1.χ calculated≤
2
χ critical,
2
that is, if the probability of deviations
it occurred by chance≥ at 5%, the null hypothesis cannot be
rejected;
2. χ 2calculatedχ critical,
2
that is, if the probability of the des-
If the occurrences are due to chance for < 5%, the null hypothesis should be
rejected, as the deviations are considered significant.
But, to reach the value ofχ critical, we 2need to calculate
the degrees of freedom (df) of the experiment. The degrees of freedom are
obtained when we subtract one unit (1) from the number of classes (k)
used in the experiment, in our case, the number of phenotypic classes
picas. Logo, for four phenotypic classes the degree of freedom (gl = k
– 1) will be equal to 3 (gl = 4 – 1). Now we just need to find the value of theχ 2

critic table of distribution of critical values ofχ , for gl = 3 and

2

α = 0.05 (Table 5.3).

SIGNIFICANCE LEVEL
When we test a hypothesis, we are willing to take the risk of rejecting it when
it is true (Type I error) with a maximum probability (P), which we call the level
of significanceαFor example, at a significance level of 0.05, we have a 5% chance
to err when we say that a deviation is significant. In other words, we have a
95% confidence that the decision to reject the null hypothesis is correct. Normally
we chose a significance level of 0.05 for most biological problems, although
other values may be used.

90C E D E R J
 DISTRIBUTION OFχ²

α 0.90 0.80 0.70 0.50 0.30 0.20 0.10 0.05 0.01

gl

1 0.02 0.06 0.15 0.46 1.07 1.64 2.71 3,84 6.64

2 0.21 0.45 0.71 1.39 2.41 3.22 4,60 5.99 9.21

3 0.58 1.00 1.42 2.37 3.66 4.64 6.25 7.82 11.34

4 1.06 1.65 2.20 3.36 4.88 5,99 7.78 9.49 13.28

5 1.61 2.34 3.00 4.35 6.06 7.29 9.24 11.07 15.09

6 2.20 3.07 3.82 5.35 7.23 8.56 10.64 12.59 16.81

7 2,83 3,82 4.67 6.35 8.38 9.08 12.02 14.07 18.48

8 3.49 4.59 5.53 7.34 9.25 11.03 13.36 15.51 20.09

9 4.17 5,38 6.39 8.34 10.66 12,24 14.68 16.92 21,67

10 4.86 6,18 7.27 9.34 11,78 13.44 15,99 18.31 23.21

DEVIATION
INSIGNIFICANT DEVIATION
SIGNIFICANT

Table 5.3: Table of distribution of critical values ofχ according to the 2

degrees of freedom (df) and the significance level
significanceα), that is, the probability (P) that the deviations are or are not significant. Modified Fisher table,
R.A. and Yates, F. Statistical tables for biological, agricultural and medical research. 6th ed. Harlow: Longman, 1974.

In the first cross, the cross of the peas that differ

as for the color and shape of the seeds, theχ calculated
2
is less than theχ 2

critical(0.22 < 7.82) and, therefore, the probability that the deviations in
the relationship to what is expected by H0 is occurring at random is greater than
5%. Thus, we cannot reject the H.0which leads us to conclude that the
results obtained in this crossbreeding are consistent with the results
expected by the 2nd Law of Mendel.
As for the result of the second crossing, involving various
of sweet pea that differs in flower color and size of
pollen, theχ calculated
2
is greater than theχ critical(832,100
2
> 7.82). In this
case, therefore, the probability that the deviations from the expected
by H0occurring by chance is less than 5%. For this reason,
we must reject H0considering that the observed result in this
The crossing does not match what is expected by the 2nd Law of Mendel.
!
An alternative hypothesis (HA) must then be suggested; for example, the
genes involved in the determination of flower color and pollen size Limitation of the test of
chi-square
sweet peas may be located on the same chromosome
This test cannot
and therefore do not segregate independently when the gametes to be applied in expe-
lifestyles in which the
They are formed. From Lesson 13 you will know more about linked genes, expected frequency
and will better understand this deviation from Mendel's 2nd Law. of any class
the phenotypic should be smaller

what of 5.

C E D E R J 91
 The chromosomal theory of
inheritance and the discovery of
sex chromosomes 6
At the end of this lesson, you should be able to:
• Understand that the construction of theory
chromosomal inheritance was the result of the accumulation of
evidence provided by various researchers in the
first decades of the 20th century.
• Describe how the sex chromosome was discovered.
• Describe how sex determination occurs in
various systems.
Describe how sex-linked inheritance was discovered.
Explain sex-linked inheritance based on the theory.
chromosomal inheritance.
Basic Genetics | The chromosomal theory of inheritance and the discovery of sex chromosomes

INTRODUCTION After the rediscovery of Mendel's work in 1900, many scientists dedicated themselves
You will attest the transmission of inheritance in various organisms. In part, beauty.
Mendels'analysiswasinthefactthatitwasnotnecessarytoknowthephysicalnatureof
Hereditary factors (HF), or how they control the phenotype, to analyze the results.
crossroads or make predictions. However, some questions remained unanswered.
tobedone:whatarehereditaryfactors?Wherearetheylocated?
The genetics of a great discovery about hereditary factors today
Known as genes, they are part of specific cellular structures, the chromosomes.
Conceptthatbecameknownasthechromosomaltheoryofinheritance(CTI).

WILLIAMBATESON ThebaptismofGeneticsandtheoriginofsomeofitsterms
(1861-1926)
WILLIAM BATESON was the one who proposed the term Genetics in 1906.
Bateson was one of
first to accept the for the new science that was being born and still did not have a name.
Mendelian laws that
were rediscovered Around 1897, Bateson began to develop experiments in
in 1900. He
hybridization with domestic birds and butterflies, and upon reading the works
popularized the
Mendelian genetics de Mendel recognized the importance of the proposed laws. In 1902,
in England,
discovered the connection Bateson translated Mendel's work into English and published it.
genetic and introduced the
term Genetics. strongly the Mendelian laws in the transmission of biological inheritance.
Anotherinterestingfactisthat,althoughwhenwepresentthework
In Mendel's terms, the words zygote, homozygote, and heterozygote are used,

they were only proposed later, also by Bateson, who still

created the term alelomorphs, now reduced to alleles.
But the creation of the terms gene, genotype, and phenotype is

credited to another important scientist, WILHELMLUDVIGJOHANNSEN.

Based on studies with beans (Phaseolus vulgaris), Johannsen
observed that individuals with the same genetic makeup

WILHELM they could present different weights due to the influence of factors
LUDVIG environmental, thus introducing the term genotype for the constitution
JOHANNSEN
organism genetics and phenotype for the presented characteristic
(1857-1927)
by the organism that depends on the interaction of its genotype with the
Geneticist
Danish that, environment. The term gene, also proposed by Johannsen, came
together with Bateson,
it was one of the main from the abbreviation of the term pangen, used by De Vries to name
architects of
Modern genetics. the discrete particles that he believed were responsible for the
Introduced the terms determination of biological inheritance.
gene, genótipo
the phenotype.

94C E D E R J
 Below is an excerpt extracted from the original text of
Johannsen where he suggests the creation of the term gene as a replacement
in the terms: factors, elements, or alleles used previously.
On this same occasion, he also proposes the terms genotype,
phenotype:

Therefore I have proposed the words 'gene' and 'genotype'

and some further terms, such as 'phenotype' and 'biotype' to be
used in the science of genetics. The 'gene' is nothing but a
very applicable little word, easily combined with others, and
hence it may be useful as an expression for the "unit factors",
"elements" or "allelomorphs" in the gametes, demonstrated by
modern Mendelian researches. A 'genotype' is the sum total
of all the 'genes' in a gamete or zygote (...)As to the nature of
the “genes”, it is as yet of no value to propose any hypothesis;
but that the notion of the 'gene' covers a reality is evident in
Mendelism. The Mendelian workers have the great merit of
[Link]
restraint - a quite natural reaction against the morphologico-
phantastical speculations of the Weismann school — it may
be emphatically recommended to use the adjectival term
Use 'genotypical' instead of the noun 'genotype'.

Johannsen, 1911

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

We assigned toWALTERSTANBOROUGHSUTTONand aTHEODORBOVERI, for your

publishedworksintheearly20thcentury,thefirstideasthatrelated
the hereditary factors to the chromosomes. Sutton, through studies with
locusts, showed that there was a parallelism between behavior
the hereditary units postulated by Mendel and the behavior of
chromosomes in meiosis and fertilization. Boveri managed to change the number of
chromosomes in sea urchins and showed that the chromosomes of a
WALTER species differ from one another and that the complete set of chromosomes
STANBOROUGH
SUTTON it is necessary for the normal development of the organism.
(1877-1916) The origin of TCH is based on indirect relationships, as Sutton and Boveri never
Graduate student they saw an FH on the chromosome, but in science, discoveries often
american when
proposed the theory Causal relations are based on the parallel behavior of phenomena.
chromosomal
of the inheritance. Currently, although the idea that genes are on chromosomes seems
obvious to us at the time, this idea was not clear, nor was it accepted by the
majority of the scientific community. Willian Bateson, one of the most prominent
geneticists were not convinced by the suggestions proposed by Sutton. And even
the [Link] BEECHER WILSONone of the most important cytologists, had

difficulty in understanding what was being proposed. And Sutton was working on
Wilson Laboratory at Columbia University!
It was necessary for various scientific evidence to be accumulated so that
the idea proposed by Sutton and Boveri was accepted above any suspicion
THEODORBOVERI and the fusion between genetics and cytology became an essential part of
(1862-1915) genetic analysis.
German biologist.

THE DISCOVERY OF SEX CHROMOSOMES

At the end of the 19th century and the beginning of the 20th century, began to

the first evidence of the involvement of chromosomes in

determination of sexes. These evidences were a point to strengthen
the idea that chromosomes are the basis of heredity.
In 1891, H. Henking published his observations about the
existence and behavior of an "accessory" chromosome during the
spermatogenesis of Pyrrhocoris sp., a species of bug. Henking
EDMUND BEECHERobservou que cada célula diplóide nos machos da espécie estudada possuía
WILSON a total of 23 chromosomes, including 11 pairs of homologous chromosomes,
(1856-1939)
in addition to an extra chromosome, which he called element X.
One of the most
important Meanwhile, the behavior of this X chromosome during the
early cytologists
of the twentieth century. meiosis seemed unusual. At the beginning of meiosis, all the chromosomes
They were duplicated, including the X chromosome. So far, so good.

96C E D E R J
But, as it did not have a homologous chromosome, the X could not be
pair and therefore only one of the two pilot cells received this
chromosome at the end of the first meiotic division.

Figure 6.1: Scheme of meiosis in male Pyrrhocoris sp. presented by

Henking in 1891. a) Spermatocyte in telophase of the first meiotic division.
Note the differentiated behavior of the X chromosome that is heading towards
the right pole is delayed compared to the other chromosomes. b) and c) Daughter cells
resulting; the X chromosome is present in only one of them.

Already in the second meiotic division, when the chromatids of each

duplicated chromosomes separated and migrated to opposite poles,
four daughter cells were formed, of which two had 11
chromosomes, while the other two had 11 chromosomes
but the X. Thus, this X chromosome was found in only half
two spermatozoa of this species of bug. However, Henking
limited itself to describing what it had observed, without creating hypotheses for

explain what was happening.

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

!
Stay alert! If you are not yet so familiar with the phases of
meiosis to the point of mentally visualizing what was described, seek
make a diagram that reflects what Henking observed. Do the same
whenever the text seems confusing. You can check your scheme
with the schemes presented in our classes or with a visit to
tutor at your location.

Another researcher of great importance for cytology in

the turn of the 20th century was Montgomery. He investigated in detail the
spermatogenesis and oogenesis of various hemipteran insects and interpreted
your results suggesting that chromosomes were cellular structures
permanent; which existed in pairs of homologues, with one of the
members of the pair were inherited from the father and the other from the mother and that the synapse

consisted of the pairing of the homologues. Like Henking, he

also described the 'accessory' chromosomes, but did not relate them
with the determination of sex.
It was then that an American cytologist, C. E. McClung (1901),
formulated a hypothesis in which the X chromosome would be associated with
some way with the determination of sex:

Assumindo que há uma diferença qualitativa entre os vários

chromosomes in the nucleus, necessarily follow that they are formed
two different types of sperm that, by fertilization of
egg, would produce two different types of individuals. Once that
the number of each of these types of spermatozoa is the same,
there should be a roughly equal number of these types of
individuals in the descent. We know that the only quality
What separates the members of a species into two groups is sex.

Doesn't this hypothesis seem quite logical? That's what many

scientists of the time also thought about it and then started to test it
through studies with various species of plants and animals.

THE WORK OF SUTTON EMBRACHYSTOLA

In 1902, Sutton published an article in which he described his

studies on the chromosomes of the testicular cells of grasshoppers
of the genus Brachystola. Based on the observations made in this work and
in the works of Henking, Montgomery and McClung, Sutton, in 1903,
published The Chromosomes in Heredity, where it shows that there is a
impressive similarity between the behavior of chromosomes and

98C E D E R J
the behavior of hereditary factors proposed by Mendel. The
Mendel's results could be explained by assuming that the factors
they were part of the chromosomes (Figure 6.2).
The basic observations of the study were:
The chromosomes of a diploid cell can be grouped
in two morphologically similar sets. That is, each
chromosome is represented twice (chromosomes
homologous). There were already strong reasons at the time to believe

that, during fertilization, a set was derived from the father

and the other from the mother.

2. Homologous chromosomes pair up in a stage of

meiosis.
3. Meiosis results in gametes that carry only one
chromosome of each pair of homologs.
4. The chromosomes maintain their individuality through the
cell division processes, despite the great changes
of the aspect they suffer.
5. In meiosis, the distribution of chromosomes from a pair
of homologs for the daughter cells is independent of the
distribution of the other chromosomes of the other pairs. If
a cell receives a chromosome of paternal origin from
a pair of homologs, may receive both the chromosome
paternal as much as maternal of another pair, being this a
probability question (Figure 6.3).

C E D E R J 99
 Genética Básica| A teoria cromossômica da herança e a descoberta dos cromossomos sexuais

Inherited chromosome
motherly

METAPHASE I
The homologous chromosomes A
duplicates and paired if A
theyalignonthemetaphysicalboard
from the heterozygous cell to the a
geneA.
a

Inherited chromosome
paternally

ANAPHASE I
1st Law of Mendel: segregation of
homologous (and their alleles), although
each chromosome remains
duplicate.

TELOPHASE I
Two cells are formed
with only one counterpart
duplicate. Following (Meiosis A a
II) the sister chromatids of each A a
cromossomo se segregam,
forming the gametes.

TELOPHASE II
Each heterozygous cell
for one gene produces 2
types of gametes. Of this
way, when we consider 1/2A 1/2a
todas as células meióticas
of the individual, 2 types of
gametes are formed in the
proportion of 1A: 1a

Figure 6.2: Segregation of hereditary factors postulated by Mendel in his first

law, assuming that they are in the chromosomes.

100C E D E R J
 1 METAPHASE I ANAPHASE I TELOPHASE I TELOPHASE II

Chromosomes of
maternal origin
1/2 Ab

1/2 aB
Chromosomes of
paternal origin

OU
2 METAPHASE I ANAPHASE I TELOPHASE I TELOPHASE II

Chromosomes of
maternal origin
1/2 AB

1/2 ab
Chromosomes of
paternal origin

METAPHASE I ANAPHASE I TELOPHASE I TELOPHASE II

2nd Law of Mendel: independent assortment 1st Law of Mendel: segregation Two cells are produced The sister chromatids of each cro-
pending between pairs of chromosomes- two homologues (and their alleles) with only one chromosome- they separate, forming
mos (already duplicated and paired) of each pair, although each me (although duplicated) of the gametes.
see the possible alignments chromosome remain du- each pair.
metaphases (1 or 2) for cells applied.
double heterozygous.

Figure 6.3: Comparison between the Law of Segregation and the Law of Independent Assortment with behavior
two chromosomes in meiosis.

Each double heterozygous cell (AaBb) can present metaphase alignment.

of type 1 or 2, producing only two types of gametes (Figure 6.3). When
we consider the set of gametic cells of an individual, it is expected that
present the alignment of type 1 and present the alignment of type 2. Thus,
In the gamete set of this individual, the four types of genotypes are expected.
in the ratio of 1AB : 1Ab : 1aB : 1ab.

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

Sutton's deductions went further. He predicted that if the hypothesis

if the proposal were correct, results different from those observed by Men-
they should have been expected, as there should have been more than one FH in each

chromosome; otherwise the number of inheritable traits of a

species would be equal to the number of its chromosomes. Sutton comments:

We must, therefore, assume that at least some chromosomes are

related to a certain number of different allelomorphs. If this is the
case, and considering that the chromosomes maintain their individuality,
The alelomorphs present on the same chromosome must be inherited.
together. If the genes of a chromosome were inherited together, there is no
I would see the possibility of independent segregation and we would not observe it,

in this case, the phenotypic proportions observed by Mendel.

Although the chromosomes were strong candidates, the analyses
those carried out by Sutton could not be considered as evidence
certain that the FH would be in these structures. The FH could be
part of some other cellular structure that had the behavior
similar to that of chromosomes during meiosis and fertilization.
The analysis of Sutton was just a first step. We will see that several
scientists continued research in this field, cementing the
chromosomal theory of inheritance and establishing the foundations of
Genetics.

SEX DETERMINATION SYSTEMS

Wilson, professor of Sutton, was one of those who became strong.

defender of Sutton's hypothesis. At first, Wilson worked in the field
of Developmental Biology, but after Sutton's publications, her
research turned to the cytological study of chromosomes and resulted
in a series of articles entitled Studies on Chromosomes.
Wilson was the main person responsible for solving the problem of the
accessory chromosomes, in 1905. Observing germ cells
of males and females of Hemiptera, he demonstrated that the differences
chromosomal differences between the sexes could be of two types and he was convinced

that there was some type of definitive relationship between chromosomes and
the determination of sex. Currently, these two types of differences
chromosomaldifferencesbetweenthesexesobservedbyWilsonareknownas
the XX/XY and XX/X0 systems of sex determination (Table 6.1).

102C E D E R J
Frame 6.1: XX/XY and XX/X0 systems for sex determination.

XX/XY System
Set
All mammals, including humans, chromosomal
diploid
têm o sexo dos indivíduos determinado pela
combination of two sex chromosomes: the
X is a non-homologous chromosome to X,
[Link] these organisms, the females Gametes
they possess a pair of homologous chromosomes
(XX) and produce, therefore, only one type
of gamete in relation to the chromosome
sexual, being called homogametic
Prole
(of the greghomoses, the same). For its part, the
males have an X like females
it is a Y chromosome, exclusive to males
and generally smaller. These males (XY)
are called heterogametic (from Greek
heteros, different) for producing two types
different from gametes, half of them containing
one X chromosome and the other half contains
of a chromosome Y.
autosomes
sex chromosomes

Set
chromosomal
System XX/X0 diploid

Some other organisms, like grasshoppers, Gametes

they have a sex determination system
similar to the XX/XY system, except for the
absence of the Y chromosome in males. As
Females are XX while males are XY.
In this case, the "zero" represents the absence of one.
sexual chromosome. However, males
they continue to be the heterogamous sex, already
that half of your sperm carry Prole
one X chromosome, while the other half
does not carry sex chromosome. In this case,
just like in the case of the XX/XY system, they are the
males that determine the sex of the individuals
from the bud.
autosomes
sex chromosome

!
How do the X and Y sex chromosomes pair during meiosis?
In the human species, only the ends of the Y chromosome have homology with the ends.
of the X chromosome (pairing regions), which allows the pairing of the X and Y chromosomes
during male meiosis. Thus, meiosis follows its normal course and the daughter cells receive
just one of the sex chromosomes.

CEDERJ 103
Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

THE DISCOVERY OF THE HERITAGE LINKED TO SEX

In 1906, Doncaster and Raynor observed a type of inheritance.

linked to sex based on a study involving crosses of two
varieties of butterflies of the genus Abraxas, the varieties grossulariata
elacticolor. The grossulariata butterflies were characterized by
they have dark wings due to the presence of large spots, while
lighter colored slats presented lighter wings, since the spots
they were minors.

When machosgrossulariata were crossed with females

lacticolor (Figure 6.4.a), only grossulariata individuals were observed.
in the spring (F1). Thus, Doncaster and Raynor concluded that the factor
condition of the state of grossularite character will be dominant (G) in
Regarding the factor that conditions the state of character lacticolor(g). You
Do you remember Mendel's experiments?
Meanwhile, when the F1 individuals were intercrossed, they
they produced the expected ratio of 3 grossulariato to 1 lacticolor
in F2, but all individuals were female — which was not
expected.
Totrytounderstandwhyonlythefemaleswerelacticolor,Doncaster
e Raynor performed reciprocal crosses, in which male lacticolor
were crossed with wild female grossulariata (Figure 6.4b)
coming from regions where the lacticolor variety did not exist, and that,
therefore, they should be pure. They observed that in F1 all the females
eramlacticolor, while all the males were grossulariata, and not the
expected of 100% of the individuals grossulariata.
Based on these observations, Doncaster and Raynor formulated
a hypothesis, a bit complicated, that provided an explanation
possible for the problem. However, this hypothesis was rejected when
the first studies with Drosophila began to emerge.
In any case, Doncaster and Raynor made two observations.
Important considerations: the existence of characters that have inheritance
linked to sex; and, that in the sex determination system of this species
of butterflies, the females should be heterozygous while
males would be homozygous. Today we know that the determination
The sex in some species of moths follows the ZZ/ZW system.
(Table 6.2) and that the gene determining the wing spots is located in the
chromosome Z.

104C E D E R J
a

Figure 6.4: Pattern of transmission of the dark spot characteristic on the wings in reciprocal crosses
between butterflies of the genus Abraxas. a) crossing between males grossulariata and females lacticolor. b)
crossbreeding between male machoslacticolore and female grossulariata.

Try to determine the genotype of the individuals presented in Figure 6.4, knowing
that the female of this moth is the heterogametic sex and that the gene for spots on the wing is
no chromosome Z. To do this, replace the '-' over the letter Z, in the diagrams on the right, with
factors (alleles) G or g correspondents. See the answer at the end of this lesson.

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Basic Genetics | The chromosome theory of inheritance and the discovery of sex chromosomes

Frame 6.2: ZZ/ZW and ZZ/Z0 sex determination systems.

Set
chromosomal
diploid

ZW/ZZ System
In many species of birds and in lepidoptera
Gametes
(butterflies), it is the males that
they have a pair of sex chromosomes
homologous (ZZ), while females have
a non-homologous pair (ZW), with one of the
chromosomes are equivalent to those of males. Note
that these sex chromosomes are named
different (Z and W) so that there is no confusion
with the XX/XY system. In the ZZ/ZW system, they are the
females that determine the sex of the individuals Prole
from the females and not the males, since they are the ones that are

heterogametic.

autosomes
sex chromosome

Set
chromosomal
diploid

System Z0/ZZ Gametes

There is also a system similar to

ZW/ZZ system. But, in this case, the females
(Z0) have only one sex chromosome
and constitute the heterogametic sex, being
the absence of chromosome W indicated by
"zero". This sex determination system
is present in some species of moths
and some other insects. Prole

autosomes
sex chromosome

106C E D E R J
HERITAGE LINKED TO X

Below Wilson's laboratory was T's [Link]

MORGAN is a remarkable group of students who, through their studies with
Drosophila melanogaster developed the foundations of Genetics.
Morgan's laboratory became the world center of Genetics.
Researchers from all over the world came to the 'fly room',
nickname given to the laboratory, for visiting or conducting research.
Throughout this and the upcoming classes, we will get to know some of the THOMAS
MORGAN
experiments developed with fruit flies by Morgan's group,
(1866-1945)
including those that became definitive evidence that the factors For its intense
Hereditary traits are in the chromosomes. I work with
Drosophila, or
laboratory of
Morgan in Columbia
University about
known as the
"room of the flies"
In 1915, Morgan,
Bridges and Sturtevant
published
Mechanism
of Mendelian
Heredity, a work
that established
definitely to
Drosophila like a
important model
experimental in
Genetics. Morgan
won the award
Nobel Prize in Physiology and
Medicine in 1933.

Figure 6.5: Drosophila melanogaster (fruit fly, banana fly or fly-

The species Drosophila melanogaster is one of the most popular organisms
experimental used in Genetics. The studies using drosophila in Genetics
they started with Thomas Morgan in the early 1900s.

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

In 1910, while washing the glasses used in experiments, a

Two of Morgan's students, Calvin Bridges, found a fly with eyes
whites (a mutant phenotype) instead of the normal red eyes of
its species (wild phenotype). This white-eyed male was crossed
com fêmeas selvagens para que o padrão de herança dessa mutação,
currently called white, was established. Morgan observed that
only individuals with red eyes appeared in the offspring, which
demonstrated that this mutation could be determined by a factor
recessive (w). When F1 was intercrossed, a phenotypic proportion
from 3 red-eyed flies to 1 white-eyed fly was
found in F2. Although, at first, this proportion may seem to be
according to the results obtained by Mendel, there was a problem:
All individuals with white eyes in F2 were males.
Morgan encountered a problem similar to that of Doncaster
Raynor, in which the inheritance of a character would be associated with sex.
to investigate further, Morgan conducted a reciprocal cross to
original, no females were crossed with wild males.
In the offspring of this cross, all the male F1 had white eyes.
and all the females had red eyes, which was not in accordance
with the expected 100% of individuals with red eyes. In F2
males and females were found, wild males and females
in the proportion of 1:1:1:1.
As Morgan noted, the inheritance pattern of the white mutation
it was the same pattern of inheritance of the X chromosome, he concluded that the

the determining factor of the white eye color should be located in the
X chromosome, that is, linked to X (XwThe male that had only
an X chromosome would have only one copy of the determining factor
of the color of the eye. This would explain the observed results. According to the

Morgan's hypothesis, in the crossing of white femaleswXw) com

wild brutesWY), all the children should have white eyes
(XwY), while all the daughters would have red eyes (XWXw) There would be,
therefore, in F2, a ratio of 1:1:1:1 of male white (XwY),
females white(XwXwwild males (XWY) and wild females
(XWXwThis hypothesis, with other characters and in other organisms,
it was extensively tested by Morgan and other researchers, and not
could be rejected.

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 FIRST SECOND
CROSSING CROSSING
a b

P P

Red White White Red

w+ w+ w w w w+

X X XY
XX XY XX

F1 gametes 1/2 1/2

F1 Gametes 1/2
w+
1/2
w

Gametes Gametes
X Y X Y
100% 1/2 1/2 100% 1/2 1/2
w+ w+ w w+ w w w+ w

X XX XY X XX XY
Red Red Red White

X X

F2 Gametes 1/2 1/2 F2 Gametes 1/2 1/2

w+ w

Gametes Gametes
X Y X Y
1/2 1/4 1/4 1/2 1/4 1/4
w+ w+ w+ w+ w+ w+ w w+

X XX XY X XX XY
Red Red Red Red
1/2 1/4 1/4 1/2 1/4 1/4
w w w+ w w w w w

X XX XY X XX XY
Red White White White

Figure 6.6: Hypothesis to explain the inheritance pattern of the white mutation in crosses between a) female of
red eyes x male with white eyes; b) reciprocal cross (female with white eyes x male with red eyes
red)

HERITAGE LINKED TO Y

Genes located on the Y chromosome are transmitted from father to

son,sinceonlymalesreceivethischromosome,andtheyarecalled
ofthegenesholandric(fromtheGreekholos,completely;andros,male).

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

A good example of inheritance linked to Y occurs in the fish Poecilia.

reticulata, where males have a more attractive ornamental coloration
the females transmit this phenotype to all the offspring. The females
this species never carries or expresses the gene.
In humans, until recently, the only gene conclusively
Located and mapped on the Y chromosome is the SRY gene.
sex-determining region Y gene). This gene plays a primary role in
determination of the embryo's sex, as it is responsible for differentiation
two testicles at the beginning of embryonic development.

!
Genome projects and the discovery of genes on the Y chromosome
Genome projects offer a great opportunity for the search for genes located in regions
heterochromatic regions of chromosomes, such as a large part of the Y chromosome in various organisms.
Heterochromatic regions are characterized by the presence of long sequences of repetitive DNA.
and non-coding DNA, making it difficult to locate genes for technical reasons. Due to its
repetitive nature, the sequencing and assembling of the sequences of these regions in the correct order
it's not that simple. Despite the difficulties, efficient computational methods have been developed.
that compare DNA sequences with protein sequences, and even with messenger RNA,
Objective to optimize the search for genes on chromosome Y. Together with experimental validation,
These methods can then reveal the existence of genes on that chromosome.

Even before the publication of the complete sequence of

human Y chromosome, more than 20 genes or gene families with
various functions have been identified on this chromosome, being expressed
in different tissues, such as in the brain and the testicles. However,
many of these genes are involved in male-specific functions,
how spermatogenesis and the determination of the male sex can
present more than one copy along the Y chromosome.
The Y chromosome of Drosophila seems to be more specialized.
for having genes related to exclusively male functions,
since the X0 males are normal except for sterility. After the
genome sequencing of Drosophila, they were identified by
less than 15 genes on the Y chromosome, most of which are related
to fertility factors or male characteristics, such as the heartbeat
from the tail of the sperm.

OTHER SEX DETERMINATION SYSTEMS

There are still systems of sex determination that do not depend on

only two sex chromosomes. Examples of this type of system are the
haploid-diploid system is the system that depends on the balance between the
number of X chromosomes and autosomes (Table 6.3).

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Table 6.3: Some systems of sex determination that do not rely solely on sex chromosomes.

Set
Haploid-diploid system chromosomal
haploid or
The sex determination system in some diploid

organisms, such as in bees, is somewhat n 2n

peculiar, because it involves the complete set normal meiosis
modified meiosis
of chromosomes. Males are produced by
parthenogenesis, from unfertilized eggs.
Gametes
When conditions are favorable, these eggs
they develop, giving rise to the drones,
what are, therefore, haploids (n) and their set n n n
chromosomal is entirely maternal. The
drones then fertilize the eggs, giving rise to
the diploid females (2n). These females can
whether they become fertile queens or infertile workers, normal fertilization parthenogenesis
depending on the type of food that they will
to receive during the larval stage. So that it Prole
we return queens, the larvae must be fed
with royal jelly. 2n n

Autosomes

Proportion Reason
Sex
X:A X/A

X:AAA 1/3 = 0.33 Metamacho

Reason X/A Macho

X:AA 1/2 = 0.5
normal
In the case of fruit flies, sex determination
depends on the reason X/A, where X represents the XX:AAA 2/3 = 0.67 Intersex
number of X chromosomes represents the
number of sets of haploid autosomes. XX:AA 1
Female
Normal females have two X and two normal
haploid sets of autosomes, being the Female
XXX:AAA 1
X/A ratio equal to 1. Normal males have triploid
only one X chromosome for two sets
autosomal haploids, at a ratio of 0.5. XXX:AA 3/2 = 1.5 Metafemale
Individuals who have a greater reason
what is called metafemales, while
individuals with a ratio less than 0.5 are
called metamachos. Already individuals with Note: In Drosophila, the Y chromosome determines the
ratios between 0.5 and 1 exhibit a phenotype fertility and not the sex of the individuals, since this
intermediary called intersex. chromosome does not have determination genes
sexual. Since Y is not essential for a
an individual becomes male, an XXY individual will be
a female, while an individual X0 will be a
sterile male.

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

Female Macho

In some
vertebrates
X1X1X2X2 X1X2Y
particularly
our mammals.
Multiple systems
Multiple systems of sexual determination are
characterized by the presence of more than one pair Majority of species
X1X1X2X2 X1X20
of sex chromosomes in at least one of the of spider.
genders. In these systems, the gender that has a
odd number of sex chromosomes is the sex Bats of the family
heterogametic. Thus, males X1X2Y,X1X20 Phyllostomatidae
XX XY1Y2
e XY1Y2, and the ZW females1W2e Z1Z2We produce and some others
more than one type of gamete. vertebrates.

Some species
ZW1W2 ZZ
of snakes can
present a
of these types of
Z1Z2W Z1Z1Z2Z2
system.

PLANTS ALSO HAVE SEX

Vascular plants have various sexual arrangements. When

the male and female sexual organs are present in the same
flower, we call the species hermaphrodite. But when these organs
they appear in separate flowers on the same plant, the species is called
monöica (means 'one house'). They are the dioecious species ('two houses'),
meanwhile, which exhibit sexual dimorphism. In these species, there are
female plants, which produce flowers containing only ovaries, and plants
males with flowers that contain only anthers. Some of the plants
dioecious organisms have a pair of associated heteromorphic chromosomes — and

probably involved — with the determination of the sex of the plant.A

A large proportion of these plants have an XX/XY system. Even the
dioecious plants that do not have visible heteromorphic chromosomes
they can have sex chromosomes.

112C E D E R J
!
How to represent the alleles of a gene
During high school, in general, we use only one letter to designate the allele of a gene.
However, there are many possible representations for these alleles. The choice of one type or another
representation is generally related to the possibility of introducing information about the
alleles from their representation.
For example, we have used uppercase letters for dominant autosomal alleles and lowercase letters for
the recessive autosomal alleles. In current terms, the gene for pea seed color has
two alleles: the dominant allele that determines the yellow color and the recessive allele that determines the
green color.
When we represent genes located on the sex chromosomes, we can use a notation
different that includes this information. For the genes located on the sex chromosome, we will use the
letter representing the chromosome with the letter representing the allele of the gene in question superscripted.
For example, the gene whose mutant allele causes hemophilia in the human species is located on
X chromosome. Let's represent the normal allele of the gene as [Link] the mutant allele Xh.
Crossbreeding with Drosophila heavily utilizes the concept of wild and mutant alleles. The alleles
Wild types are those that occur with high frequency (greater than 99%) in the natural population. The
Wild alleles are generally represented by the symbol (+) or by the initial letter of the mutant allele.
with + superscript. For example, there is an autosomal gene in D. melanogaster that when the allele
mutant presented in homozygosity results in the phenotype vestigial wings. The mutant allele can be
represented by the wild allele (normal) byvg+, or simply, +. Following the same pattern
for genes on the sex chromosome, in the example of the white mutation we can have other representations
besides the one shown above for the wild allele: Xw+ or X+.
Other notations will be presented throughout the course.

Let's check the res-

exercise posts of the
Figure 6.4?

INFORMATION ABOUT THE NEXT CLASS

In our next class, we will revisit Mendel's work. We will see

how the development of Cytogenetics and Molecular Biology allowed the
understanding the physical nature of the factors proposed by Mendel, which today
we know as genes, and the mechanisms of their transmission.

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Basic Genetics | The chromosomal theory of inheritance and the discovery of sex chromosomes

SUMMARY

Genetics took a big step with the discovery that hereditary factors,
today known as genes, are part of specific cellular structures, the
chromosomes. A concept that became known as the chromosomal theory of
inheritance. At the end of the 19th century and the beginning of the 20th century, they began to emerge
first evidence of the involvement of chromosomes in the determination of sexes.
These evidences were another point to strengthen the idea that chromosomes
are the basis of heredity. The relationship between Mendel's Laws and the way in which
The gametes are formed during meiosis and can then be established.

There are several sex determination systems: systems where there is only one
a pair of sex chromosomes and the male is the heterogametic sex, XX/XY, XX/X0;
systems where there is only one pair of sex chromosomes and females are the sex
heterogametic, ZZ/ZW, ZZ/Z0; systems where there is more than one pair of chromosomes

sexual (multiple systems), such as, for example, X1X1X2X2/X1X2Y.

Many of the characteristics of a species can be conditioned by genes.

located on the sex chromosomes. The best way to find out if a
phenotype is linked to sex, that is, if the gene that conditions this phenotype
it is located on one of the sex chromosomes, through reciprocal crossings with
individuals of wild type phenotype. If the allele that determines the mutant phenotype

is related to sex, the phenotypic proportions in the offspring of these crosses will be
distributed unevenly between the sexes.

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 EXERCISES

Fill in the blanks in the numbered sentences from 1 to 8 using the term
most appropriate among those listed below:

autosome b) sex chromosomes

sex-linked inheritance limited inheritance to sex
recessiveness Hollandic inheritance
dominance h) codominance

1. ( It is the phenomenon by which one allele prevents the expression of another allele.
of the same gene.

2. ( ) is any chromosome other than the sex chromosomes.

3. The chromosomes related to the determination of an individual's sex

are called ).

4. The expression of a characteristic (for example, egg or milk production)

restricted to only one of the sexes is called ).

5. The genes located on the Y chromosome follow a pattern of inheritance.

called ).

6. is the phenomenon by which an allele does not manifest phenotypically,

however, it maintains its individuality.

7. The genes located on the X chromosome follow a pattern of inheritance.

called ).

8. ( is the situation in which both alleles of a heterozygous individual are

they also manifest in the phenotype.

Use the alternatives below to answer questions 9 and 10:

sex-linked recessive inheritance.

autosomal recessive inheritance.
(c) sex-linked dominant inheritance.
autosomal dominant inheritance.

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Basic Genetics | The Chromosomal Theory of Inheritance and the Discovery of Sex Chromosomes

9. In the crossings between female fruit flies with short wings and male flies with wings

Longas, all male descendants exhibited short wings and all females,
long wings. A reciprocal cross (female long wings with male wings
shorts) produced only descendants with long wings, both males and females.
These results suggest the hypothesis that the short-winged character state follows a
standard of ( ).

10. Black rams crossed with white sheep produced only descen-
white teeth, of both sexes. Some reciprocal crossings produced
only males and white females, while others produced half of the
white descent and half black, of both sexes. These results allow
raising the hypothesis that the state of the black wool character in sheep follows
a pattern of ( ).

A man affected by a certain illness marries a woman who is not affected.

They have eight children (four girls and four boys); all the girls have the
father's disease, but none of the boys have it. It is probably a
inheritance case __________________________.

12. In mice, a dominant sex-linked allele B is responsible for

short and twisted tail phenotype, while its recessive allele is responsible for
[Link]-tailedfemaleiscrossedwithamale
of short tail, what phenotypic ratio should be expected in the F generation?1?

13. The allele (miniature) that determines short wings in Drosophila melanogaster
it is recessive and sex-linked. Its dominant allele + determines the formation of wings
longas. What phenotypic proportions can we predict in the following crosses:

a) short-winged males X short-winged females.

b) female with short wings X males with long wings.
c) female with long wings (homozygous) X male with short wings.

In poultry, the dominant allele B, which is sex-linked, produces feathers with

Standard barred. Its recessive allele b, in homozygous form, produces only unbarred.
The dominant autosomal allele produces a crest with a pink shape and its recessive allele.

produces a crest with a simple shape when homozygous. A female with feathers.
barred,homozygousforChristwitharose-shapedcrosswithabunchoffeathers

non-barred and crest with simple shape. What is the expected phenotypic ratio in
F1 generation? Find out what the sex determination system is in birds.

116C E D E R J
 Chromosomes, genes, DNA:
a current view of the factors
Mendelian 7
By the end of this class, you should be able to:
Recognize the physical nature of the factors of
heredity.
• Relate the concepts of DNA, gene, and
chromosome
Understand how genetic material is
organized.

Prerequisites
Structure and replication
do DNA.
Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

THE CURRENT INTERPRETATION OF THE PROPOSED FACTORS

FOR MENDEL

In previous classes, we learned about Mendel's work and had

opportunity to observe the elegance with which he formulated hypotheses
to explain the transmission of biological inheritance in the mid-century
XIX. For Mendel, plants had determining factors of their
hereditary characteristics that were passed from one generation to
other through the gametes. Although Mendel proposed the
the existence of these factors, he had no idea of their nature
physics and, much less, how these factors were capable of determining
the phenotype.
You should also remember that, right at the beginning of the 20th century,

comparing the behavior of chromosomes during meiosis

with the laws of segregation and independent assortment (1a. and 2alaws of
Mendel), Sutton proposed that hereditary factors should be in the
chromosomes. This idea was not immediately accepted by the entire community
scientific, only after many studies and a great accumulation of evidence,
Around 1920, the idea that the factors was definitively accepted.
they were in the chromosomes. In the mid-1940s, it was concluded
the conclusion that DNA was the hereditary material and that in some way
form controlled protein synthesis. In 1953, it was proposed that
model that explains the structure of DNA and, at the beginning of the 1960s,
the genetic code has been deciphered. From there, numerous studies on the
The organization and functioning of genes have been developed.
Currently, we refer to the hereditary factors suggested by
Mendel of the genes and we know their nature. Each gene, unit
physical and functional of heredity, is a segment of a molecule
DNA (deoxyribonucleic acid) that contains the information
necessary for the production of an RNA (ribonucleic acid) or
a protein. Figure 7.1 presents the model of the DNA structure
but I currently accept.

118CEDERJ
 a b

Figure 7.1: Structure of the DNA molecule: the DNA molecule is made up of
by two long filaments (chains) rolled over each other forming
a helical structure (double helix). Each of the DNA strands con-
is composed of thousands of nucleotides linked in sequence. The two chains of
deoxyribonucleotides that form the DNA molecule remain united
through hydrogen bonds between the nitrogenous bases. These bonds
occur between specific base pairs: adenine (A) binds to thymine (T) and
cytosine (C) binds to guanine (G).
(a) Flat representation of the molecule, showing the hydrogen bonds
among the nitrogenous bases. The letter S represents the sugar (deoxyribose)
that links to each of the nitrogen bases, forming the "skeleton"
of the DNA molecule. (b) Representation of the double-helix structure of
DNA molecule.

THE ORGANIZATION OF GENETIC MATERIAL

So, what is the relationship between genes, DNA molecules and

thechromosomes?
VariousgenesaredistributedalongtheDNAmoleculesthatcons-
we are mapping the genome of an organism. In general, we can say that,
a gene corresponds to a segment of the DNA molecule that is trans-
written in an RNA. Some genes are transcribed giving rise to RNA
nuclear, ribosomal RNA or transport RNA. Others, give
origin to messenger RNAs (mRNAs) that, in turn, are translated
two in polypeptides (Figure 7.2a). In eukaryotes, the structure of a
The transcripted gene in mRNA is formed by two distinct types of regions.
Figure 7.2b: exons, coding sequences that contain the information
tion for the production of protein; and the introns, non-coding sequences
Introns that are inserted between the exons and need to be removed beforehand.
of the translation, through a mechanism called processing of
mRNA. As for prokaryotes, the vast majority do not have introns.

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

The processes of transcription, translation, and processing of

mRNA will be addressed in more detail in the Biology course.
Molecular.
DNAmoleculesaregeneralyquitelong,potentialyreaching
severalcentimetersinlength.
Surprisingly, the genes correspond to a quantity
relatively small part of the DNA molecule. Most of the DNA
it is never transcribed into RNA and does not contain information for production

of protein. In the human species, for example, it is estimated that only

about 3% of DNA corresponds to genes. The remaining 97% are
nucleotide sequences that do not produce RNA and whose function is still
is not known, constituting non-coding DNA. However, much
non-coding DNA can play very important functions
in the structure, function and evolution of the genome.

Genes
Gene1 Gene2 Gene3

Transcription

mRNA1 mRNA2 mRNA3

Translation

Protein1 Protein2 Protein3

Gene

Gene1 Gene2 Gene3 Gene4

Éxon1 Éxon2 Éxon3

Intron1 Intron2

Figure 7.2: (a) Simplified scheme of a segment of a DNA molecule containing 3 genes;
(b) structure of a gene.

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 Each DNA molecule is associated with a series of proteins,
forming what we call chromosomes. This mixture of DNA and
proteins that make up chromosomes are called chromatin. The
chromatin can assume different levels of compaction, depending
from the chromosome region and the phase of the cell cycle.
In vitro studies using different concentrations of salts in
chromatin treatment allowed the construction of a model for
the compaction of DNA (Figure 7.3). This model includes four levels
progressives:
1. The formation of nucleosomes by the association of DNA with
special proteins called histones: each nucleosome is formed
when the DNA wraps twice around a histone complex,
being this complex an octamer composed of two molecules of each
type (H2A, H2B, H3, H4);
2. The coiling of nucleosome chains, forming a
structure known as solenoid: the nucleosomes coil
forming the solenoid, which is stabilized by another type of histone
(H1);
3. The formation of loops from the solenoid that connect to a
non-histone protein framework;
4. The super-helicoidization of the protein framework to which the loops
of the solenoid are associated: super-helicoidization can be more or
less relaxed depending on whether the chromosome is in interphase
or in cell division. During cell division, the super-helicoidization
it is intensified until the chromosome takes on the appearance of a rod
compact

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

Nucleosome(10nm)

Histone H1

Histone forming
octomer

D NA
(2nm)

Solenoid
(30nm)

Solenoid hooks

Binding proteins
(non-histone)

Super-helicoidization

Figure 7.3: (a) Compression of the DNA molecule.

(b) Aspect of the duplicated chromosome and at its level
maximum compression during cell division.
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THE GENETIC MATERIAL IN THE INTERFACE

During this phase, the chromosomes of eukaryotic organisms

we present ourselves as long threads, forming a mass where there is no
can identify each chromosome individually. It was this mass of
very fine threads that originated thermochromatin (from Greek chromatos, color),

created in the mid-19th century, when cytologists discovered that

certain fabric dyes stained the cell nuclei.
As we saw, in some regions, the chromosomal filaments
are folded in a more compact way. These regions have an aspect
denser when observed under the microscope, being referred to as
heterochromatin (hetero = different). Heterochromatin contrasts with
regions where the filaments are less condensed, referred to as
euchromatin (eu = true).
The heterochromatic regions remain condensed during the
major part of the cell cycle. Generally, they are regions that have greater
affinity for most cellular dyes, becoming darker,
hence the name heterochromatin.
Apparently, these regions have the same properties.
in all animals and plants: they have a large amount of DNA
repetitive; almost do not undergo recombination; possess small quantity-
gene data; its replication occurs later during the cell cycle,
compared to the euchromatin region.
Heterochromatin can be divided into constitutive and facultative.
Facultative heterochromatin differs from constitutive heterochromatin by its ability to,

eventually, take on a structure similar to that of euchromatin.

Still in interphase, the cells that will divide duplicate.
your genetic material. The duplication of chromosomes occurs during the period
The interface corresponds to the replication of DNA molecules that
these chromosomes (Figure 7.4). We know that replication of
one DNA molecule gives rise to two identical molecules (except for the
in case of any error during replication). Thus, each chromosome
duplicate is composed of two identical strands, joined by the region of
centromere. Each of the strands is a chromatid. Thus, after duplication
In each chromosome, it is composed of two molecules of DNA.
identical, sister chromatids, united by the centromere region.

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

Bridges of
Hydrogen

Beginning of
deselicoidization
Connections
covalent b

New filaments
duplos
The duplication is
complete

Figure 7.4: DNAreplication and chromosomes.

(a) The model shows that DNA replication is semiconservative, producing two molecules identical to the molecule of
DNAoriginal.
(b)ModelpresentingtherelationshipbetweenDNAreplicationandchromosomeduplication.
After duplication, the sister chromatids remain joined by the centromeres until the process is complete.
cell division (the shading marks the centromeric region).

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 The Genetic Material During Cell Divisions

When the cell enters the process of division, each filament that
composes the chromosome (chromatid) coils upon itself, becoming
progressively shorter and thicker, until it takes on the appearance of a rod
compact. Each chromatid condenses independently from its sister,
so that, in the dividing cell, each chromosome can be visualized
consisting of two rods connected by the centromeres.
In general, when we talk about chromosomes, this is the image we have.
in mind. But it is worth emphasizing that the threads that make up chromatin are

the chromosomes that, in interphase, are not at their maximum degree of

compression, cannot be viewed as individual structures.
In Figure 7.5, we have a chromosome with the appearance it presents.
during interphase and another during metaphase. The difference is that in
in metaphase the chromosomes are at their maximum level of compaction,
what allows their visualization as independent bodies. Additionally,
As they are in the metaphase of mitosis, the chromosomes are already aligned.

duplicates, presenting two chromatids.

a b

Figure 7.5: Electron photomicroscopy of the chromosome in interphase (a) and during metaphase of mitosis (b).

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

CENTROMERES AND TELOMERES

Every chromosome has a constriction called cent-

primary trimerization constriction. This consists of a region of the DNA res-
responsible for the segregation of the replicated chromosome to the daughter cells

during cell division (Figure 7.6a). If a chromosome loses its

central region, segregation will not occur, the chromosome is lost
and can be degraded by the cell. In the centromere we also find
a protein disk, the kinetochore, to which the filaments attach
achromatic spindle during the cell division process.
The position of the centromere (Figure 7.6 b) delineates two arms in the

chromosome. Depending on the ratio between the size of these arms,

r = l/c, where l is the length of the long arm and c is the length of the arm.

in short, chromosomes can be classified into:

Metacentric: centromere located approximately in the middle

of the chromosome, forming two arms of similar length;
1.00 < r < 1.49.
Submetacentric: the centromere is slightly displaced from
median region of the chromosome, forming two arms of
different sizes; 1.50 < r < 2.99.
Acrocentric: the centromere is very close to one of the extremes
midpoints of the chromosome, forming one long arm and another
very small; 3.00 <r.
Telocentric: the centromere is at one of the ends,
adjacent to the telomere, having a single visible arm. Not
it occurs in the human species, although it may be present in
other animal species.

The terminal regions of chromosomes are called telomeres.

Telomeres are regions of DNA composed of repetitive sequences.
of nucleotides. It has been known for some time that these are regions
specialized that prevent two chromosomes from joining through
its extremities. In experiments where the use of X-rays caused
the loss of the telomeric region, the chromosomes showed a tendency
to connect by these ends.

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 Telomeres Figure 7.6: The compacted chromosome.
a a. Drawing of a duplicated chromosome, showing each
oneofitsparts.
b. Different forms of chromosomes, according to the position
fromitscentromere.

Primary constriction
(centromeres)

Chromatids

Telomeres

Metacentric Submetacentric Acrocentric Telocentric

b (centromere in centromere (centromere close to a (centromere in a
central position displaced from the center the extremities) the extremities)

!
In addition to the genetic material contained in the nucleus (nuclear genome), the
Mitochondria also contain DNA. The human mitochondrial genome
contains 16,569 pairs of DNA bases, including 37 genes that code
some of the proteins and RNAs involved in mitochondrial activity. The
human cells can contain thousands of mitochondria; therefore, thousands
of copies of the mitochondrial genome. This genome is inherited almost
only from the mother. This is because, during the formation of the zygote, the sperm
contributes with your nuclear genome, but not the mitochondrial one. In turn, the
the ovum contributes with its nuclear genome and its mitochondrial genome,
which is transmitted only through the cytoplasm of the maternal ovum. In
In Lesson 12, you will be able to study the inheritance of extranuclear genes with
more details.

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

THE CHROMOSOMES IN SPECIES

The nuclear genome of a species is defined as the information

total genetics present in your chromosomes.
In species that have sex chromosomes, the number of types
of chromosomes (or DNA molecules) of the species may be different from the
number of chromosomes in the haploid genome. The human species is a
good example. Although our haploid genome has 23 chromosomes
(Figure 7.7), our species has 24 different types of chromosomes,
there are 22 types of autosomal chromosomes and 2 types of sex chromosomes
sexually, the X chromosome and the Y chromosome.

a b

1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

13 14 15 16 17 18 19 20 21 22 X or Y 13 14 15 16 17 18 19 20 21 22 X

Figure 7.7: Haploid genome in the human species.

spermatozoon.
b) ovum.

128CEDERJ
 Table 7.1 shows the number of chromosomes in the genome
haplóide de diversas espécies. Como você pode verificar, onúmero de
chromosomes are not related to size or complexity
biological of an organism.

Table7.1:Numberofchromosomesthatmakeupthehaploidgenomein
some eukaryotic species.
Haploid number of
Organism
chromosomes

Mushrooms

Baker's yeast
16
Saccharomyces cerevisiae

Bread mold (Neurospora crassa) 7

Plants

Corn (Zea mays) 10

Tomato
12
Tomato

Broad bean (Vicia faba) 6

Giant sequoia
11
Sequoia sempervirens

Invertebrate animals

Fruit fly
4
Drosophila melanogaster

Mosquito (Anopheles culicifacies) 3

Starfish (Asterias forbesi) 18

Vertebrate animals

Human being (Homo sapiens) 23

Chimpanzee (Pan troglodytes) 24

Dog (Canis familiaris) 39

Cat (Felis catus) 19

Mouse (Mus musculus) 20

Frog (Xenopus tropicalis) 10

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

Genetically equivalent chromosomes, that is, presenting the

same sequence of genes, are called homologous chromosomes (from Greek
homos, igual, semelhante). Nas espécies diplóides, são cromossomos
homologous those members of the same pair. Although they have
same genes, the homologous ones do not necessarily code for the same
genetic information. Each of the homologs can have an allele.
different from the same gene, producing different proteins with effects
different in the organism. More details about alleles, their products and their
origins will be seen in Lesson 8.
Figure 7.8 shows the karyotypes of some species
of plants and animals. We call karyotype the chromosomal constitution
of a cell or of an individual. Different techniques for observation
Karyotypes have been developed and you will have the opportunity to
get to know them better in future classes. The technique presented in Figure 7.8
it's one of the simplest; coloring the chromosomes evenly, it
allows you to identify the diversity of size, shape, and number
of chromosomes in different species.

a
b

Figure 7.8: Karyotypes

of various species
(out of scale).
broad bean
Marmosa cinerea (marsupial);
(c)Felis catus(cat).

130CEDERJ
 INFORMATION ABOUT THE NEXT CLASS

Now you know a little more about the physical nature of the factors of
Mendel and how they are organized. In the next class, we will see how genes
giving rise to the phenotype and how variants emerge for the same one
gene. We will also see how the relationship of dominance between the alleles occurs.

of the same gene. In short, what they represent, in molecular terms,

the actions (A) and azinhos (a), so used in Genetics.

RESUME

Although the traditional concept of gene is under discussion, in general,

we can say that each gene is a segment of a DNA molecule that
contains the necessary information for the production of an RNA or a
protein. Various genes are distributed along the DNA molecules that
constitute the genome of an organism. Each DNA molecule is associated with
a series of proteins, forming what we call chromosomes.

During the interphase of eukaryotic organism cells, the chromosomes

they appear as long threads, forming a mass where it is not possible
identify each chromosome individually.

Still in the interphase, the cells that will divide duplicate their material
genetic. The duplication of chromosomes occurs in the S phase of interphase and
corresponds to the replication of the DNA molecules that form these chromosomes.
When the cell enters the division process, each filament that makes up the
chromosome (chromatid) coils around itself, progressively becoming
shorter and thicker, eventually taking on the appearance of a compact rod. Each chromatid

it condenses independently from its sister, so that, in the dividing cell,

each chromosome can be visualized as two rods joined by
centromere.

We call a genome a complete set of chromosomes of the species.

organisms can contain in their somatic cells one, two, three or more
sets of chromosomes.

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

ACTIVITY 1: BUILDING A INTERPHASE CELL MODEL

A. Let's imagine a hypothetical species, diploid with 2n = 6 chromosomes.

You must build a model that represents the nucleus of a somatic cell.
of an individual of this species during G1 phase of interphase. Also consider the
characteristics listed below for the construction of your model:

1. The chromosomes will be referred to as chromosome 1; chromosome 2 and

chromosome 3. Chromosome 1 is the largest of all and metacentric;

chromosome 2 is of intermediate size and is submetacentric and the
chromosome 3 is the smallest acrocentric;

2. Chromosome 1 has 4 genes, named A, B, C, and D; chromosome 2

It has 4 genes, named E, F, G, and H; and chromosome 3 has 2 genes.
named I and J;
3. The genes A and B are on one of the arms of chromosome 1 and the genes C and D on the

another arm;
4. The E gene is on the short arm of chromosome 2 and the F, G, and H genes are on the

long arm of this same chromosome;

5. Genes I and J are on the long arm of chromosome 3;

6. The individual whose nucleus will be represented is homozygous dominant for the
genesA, C, F and J; it is recessive homozygous for genes B and E and heterozygous for

all other genes. The dominant alleles of each gene will be represented
by uppercase letters and the recessive ones by lowercase letters.

As a suggestion for building your model, you can use the following
material:

• 1 hollow styrofoam ball about 4cm in diameter cut in half;

50cm of wool or string;

• labels of about 0.5cm x 1cm;

The styrofoam ball will represent the nucleus, bounded by the nuclear membrane.
The wool or string threads will be used to represent the chromosomes. And the
labels will delimit the regions of the chromosomes where the genes are located.
The centerometers will be delimited by a knot in the wool or string threads.

132CEDERJ
The material mentioned above is just a suggestion. You can use your creativity and
assemble your model with the material you find most convenient. The most important
is that you keep in mind that the model intends to be a representation of the vision
what we have about a certain theoretical concept. Often, when building a
model, we simplify the object or process to be represented, aiming to prioritize
the understanding of a more general idea. But we must always be careful to
that our models do not induce conceptual errors in other people that may
come to use them.

Therefore, before building your model, review the concepts about the core.
Interphase and the organization of the genome. Think about what each material used
will be representing and describe this, creating, in addition to the model, a sheet of

guidance for understanding it.

B. Now imagine that you obtained a preparation with the chromosomes of this
individual in the metaphase of mitosis. Draw the observed karyotype.

Check in your course guide when you should present your model.
for discussion with your colleagues and tutors.

ACTIVITY 2: ASSEMBLY OF HUMAN KARYOTYPE (2n = 46).

Figure 7.9 shows the chromosomes of a human cell obtained from

lymphocyte culture. The technique used includes the following steps:

Blood withdrawal;

2. Separation of leukocytes;

3. Transfer of leukocytes to a culture medium containing division inducers

cells (phytohemagglutinin);

4. Cell culture for a few days;

5. Addition of colchicine to block mitoses in the metaphase stage;

6. Addition of hypotonic solution to make the cells more turgid

(swollen);

7. Centrifugation for precipitation of leukocytes;

8. Collection of leukocytes and dropping onto a microscope slide;

9. Giemsa staining.

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

From the preparation described above, a cell was selected and photographed.
Each chromosome is made up of two chromatids, as the cell was in
mitosis process when it was fixed. For karyotype analysis, the next
the step is to cut out each of the chromosomes from the photograph and assemble them according to the

classification of human chromosomes. Your task will be:

1. conduct a research on how human chromosomes are classified and

how karyotype arrangements are made;

2. cut and assemble, gluing onto a sheet of paper, the chromosomes from the figure
7.9 according to the standard used for assembling the human karyotype;

3. indicate whether the analyzed cell is from a female or male individual

and if this individual has the normal number of chromosomes for the species
human.

134CEDERJ
Figure 7.9: Photograph of the chromosomes of a human cell stained with Giemsa solution in the phase of
metaphase of mitosis.

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Basic Genetics | Chromosomes, genes, DNA: a current view of Mendelian factors

ACTIVITY 3: RELATING GENES, CHROMOSOMES, AND MEIOSIS

1) Complete the meiosis diagram of a diploid cell from a male

heterozygous for the CeD genes, located on autosomal chromosomes
different. Additionally, a recessive allele for is located on the X chromosome
the geneE.

2) Now answer:

• quantos tipos de gametas foram formados ao final da meiose desta célula?

• how can other types of gametes be formed in the same individual

(CcDdXeY)?

3) Indicate all types of gametes that this individual, with genotype CcDdXeY,
it would form. And if it were a female CcDdXEX e, what types of gametes would it be

formed?

136CEDERJ
 From gene to phenotype 8
By the end of this lesson, you should be able to:
• Clarify relations between Mendelian Genetics
and Molecular Biology.
Understand the molecular bases of
determination of the phenotype.

Understand how variations arise

in the genotype and how they determine the
variations in phenotype.

Prerequisites
Structure and Duplication
do DNA.
Mechanism of synthesis
of proteins - transcription
the translation.
Basic Genetics | From gene to phenotype

REVIEWING THE TRANSCRIPTION AND THE TRANSLATION

In the Molecular Biology course, you will have the opportunity to

deepen your knowledge about the molecular organization of genes and
the processes of transcription and translation. However, we need to remember to
some fundamental concepts of these processes to understand this class.
You must remember that genes are segments of the molecule.
the DNA responsible for storing and transmitting information
genetics. According to the central dogma of Molecular Biology,
genetic information flows from DNA to DNA (replication process)
during its transmission from generation to generation and of DNA to
protein during its phenotypic expression in an organism. Most
two genes contain information for the synthesis of messenger RNA
(mRNA) —transcription process— which, in turn, will contain the
information for protein synthesis — translation process.
In the late 1950s, scientists demonstrated the
triple nature of the genetic code - each amino acid of a
protein is specified by a sequence of three pairs of nucleotides
no DNA. Soon after, the genetic code was deciphered and demonstrated-
the correspondence between the nitrogen base pairs of the mRNA
(códons) e os aminoácidos nas proteínas. O código é inequívoco,
each codon corresponds to a single amino acid, and degenerate,
because almost all amino acids have more than one codon. You
find the table with the genetic code at the end of this lesson.

…ATCATC TTT GGT GTT ... - fits sense

DNA
...TAG TAG AAA CCA CAA ... - anti-sense fit
(mold for mRNA)

mRNA ...AUC - AUC - UUU - GGU - GUU...

PTN ... ILE- ILE- PHE- GLY- VAL...

138C E D E R J
 But there are also those genes that encode for nuclear RNA
(snRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA), and
none of these RNAs are ever translated.
A summary of the transcription and translation processes is presented.
Figure 8.1.

Figure 8.1: Diagram showing a summary of the transcription and translation processes.
The structures are not to scale.

C E D E R J 139
Basic Genetics | From gene to phenotype

!
OstRNAs are small RNA molecules that function as adapters
entre os aminoácidos e os códons do mRNA durante a tradução.
rRNA are structural components of ribosomes, cellular organelles
responsible for translating mRNA into proteins.
OsnRNAs are structural components of spliceosomes, nuclear structures
responsible for removing the introns from the pre-mRNA sequences.

In our prokaryotes, the products of transcription, transcribed

primaries, in general, are equivalent to the mRNA molecule to be
Translated. In eukaryotes, the primary transcripts of many genes
contain specific sequences that must be removed for the complete
formation of mRNA, hence they are called pre-mRNA. The processing
the pre-mRNA includes the removal of non-coding nucleotide sequences
coding regions, called introns, that are inserted between the sequences
Codifying calls of the genes' exons. The removal of introns is carried out
by macromolecular structures called spliceosomes (in English
splicing). In addition to the excision of introns, the processing of pre-mRNA
mRNA includes modifications at both ends: capping
from the 5' end and the polyadenylation of the 3' end.

Gene A
site of site of
5' excision 3' excision

DNA Exon 1 Intron Exon 2

TRANSCRIPTION
Pre-mRNA
(primary transcript)

Covering 5'

m'G PROCESSING
of pre-mRNA
3' Polyadenylation in mRNA

m'G AAAAA...

Excision
mRNA
(mature transcript) m'G AAAAA...
Exon 1 Exon 2

TRANSLATION

PROTEIN A

Figure 8.2: Processing of pre-mRNA into mRNA, including the excision of intron sequences and
modifications at both ends of the primary transcripts.

140C E D E R J
 As a result of mRNA translation, we have the synthesis of
polypeptides (sequences of amino acids linked by peptide bonds).
One or more associated polypeptides form macrostructures that
we call proteins. Proteins perform numerous functions in
cell, being able to participate in the structure of organelles or in the control of

chemical reactions (enzyme proteins or simply, enzymes).

The function of a protein is ultimately determined by its
amino acid sequence (aa), which, as we have seen, depends on the sequence
of the nucleotides of its corresponding gene. Changes in the sequence
DNA nucleotides can alter the amino acid sequence, causing the
loss or modification of protein function.

REVISITING MENDEL'S PEAS

Returning to the peas studied by Mendel, today we know that the

species Pisum sativum is a diploid species, with 2n = 14 chromosomes.
This means that this species has 7 types of chromosomes or molecules.
of different DNA that appear in double dose. In one of those
chromosomes, there is a gene responsible for determining the characteristic
texture of the seed. But how does this happen?
Fortheseedstobesmooth,asubstantialpartoftheglucosecontained
our cotyledons must be transformed into large starch molecules
the branched amylopectin. The synthesis of branched starch depends on a protein

enzymatic called SBE-I (from English Starch-Branching Enzyme). And the

the synthesis of this enzyme depends on the transcription and translation of a segment

of DNA, with 3,300 base pairs, located in a region

specify one of the chromosomes of the pea. We will call this version
of the gene that conditions the synthesis of the functional enzyme SBE-I of allele R.

GeneSBE-Inormal
(DNA segment with 3,300 base pairs – allele R)
TRANSCRIPTION

mRNA

T R A N S L AT I O N

functional enzyme protein SBE-I

ENZYMATICREACTION

Glucose --------------- branched starch

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 Basic Genetics | From gene to phenotype

But there is another version of this gene, because this segment of

DNA can have its nucleotide sequence altered by the insertion of
800 pairs of nucleotides. This altered form of the gene does not produce the

Alelo functional SBE-I enzyme, being a Alelonon-functional of this gene that

The term allele is we will call alelors (Figure 8.3).
used to identify
different versions of
the same gene, or
be, small
GeneSBE-Icom the insertion of 800 nucleotides in its sequence
variations of one
(DNA segment with 4,100 base pairs – alleles)
DNA segment.
TRANSCRIPTION

mRNA

T R A N S L AT I O N

non-functional enzyme protein SBE-I

NOENZYMATICREACTIONOCCURS

Glucose ----------------------------- branched amylopectin

a b

NORMAL ALA MUTANT ALLELE

R r

Insertion of a
segment of 800
nucleotides

DNA
TRANSCRIPTION

mRNA
TRANSLATION

FUNCTIONAL SBE-I PROTEIN NON-FUNCTIONAL SBE-I PROTEIN

GLUCOSE BRANCHED STARCH

Figure 8.3: Molecular origin of the change in the shape of the pea seed. The wrinkled phenotype results from the insertion-
chain of nucleotides in the gene that codes for the SBE-I protein, responsible for starch synthesis
ramified from glucose. (a) normal allele; (b) mutant allele.

142C E D E R J
 Plants with wrinkled seeds have a genotype. That is, the
two chromosomes of the homologous pair that has the DNA sequence
The gene that encodes the SBE-I protein has the version of this gene. We have already seen that

the ale produces a protein that is not able to catalyze the reaction that
transforms glucose into branched starch, resulting in an accumulation
of sucrose, increasing the osmotic pressure inside the cells of the
cotyledons. Consequently, the cells of the cotyledons absorb and
they accumulate a large amount of water during their development.
With the maturation of the seeds, there is a loss of a large quantity.
of water, which causes the wrinkling of its skin.
The plants that have at least one copy in their genotype
of aleloR(RRouRr), the version of the gene capable of synthesizing the enzyme

SBE-I functional, synthesize branched starch and are in the cells of

Cotyledonshavelowerosmoticpressure,[Link]

they mature, their cotyledons lose very little water, maintaining-

they are practically the same size and, therefore, do not wrinkle their
shell. Note that in this case, the presence of a single allele produces a
sufficient amount of the enzyme for the transformation reaction of
glucose in branched starch occurs at the necessary levels for
the shape of the seed is smooth (Figure 8.4).

GENOTYPE R/Homozygous R/r heterozygous r/rhomorozigoto

Protein No
Functional Functional
Functional
mRNA

Chromosomes
homologs
Chromosomes aleloR AleloR of them
homologous aleloR of the wing of the singers

mRNA

Protein No No
Functional
Functional Functional

Phenotype
Pea Pea Pea
lisa lisa rugosa

Figure 8.4: The molecular bases of Mendel's factors.

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Basic Genetics | From gene to phenotype

HOW DO NEW ALLELES EMERGE?

In the example of the seed texture in pea, we used the letters

Reassign the two alleles responsible for the determination of
variation of this characteristic. We saw that the difference between these alleles
it is in the difference between the nucleotide sequence of the DNA segment
which encodes the enzyme SBE-I. The allele has 800 base pairs more than
that the allele RNA its sequence. Bhattacharya and collaborators, in 1990,
they published a paper in which they show that this difference originated
the insertion of a transposition element in the SBE-I gene results in
alelora starting from the aleloR. We then say that the gene SBE-I underwent a

mutation, that is, a change in its nucleotide sequence.

!
Transposable elements (or transposons) are segments of DNA that
have the property of changing position in the genome. When the elements
they move from one place to another during transposition, they may break
chromosomes or mutate genes, thus having an important meaning
genetic.
The first account of the existence of transposition elements was
published in 1948 by the American scientistBARBARAMCCLINTOCK, that
devoted a large part of his life to corn genetics research.
At first, your ideas about the possibility of segments existing
the DNA that changed places was not well accepted. The concept of
BARBARA transposition contradicted the established point of view that genes
MCCLINTOCK they occupy fixed positions on the chromosomes. In the decades of the 1960s and 1970s,
transposition elements have also been observed in bacteria and
in drosophilas, and today we know that they occur in many species, including
in the human species. McClintock won the Nobel Prize in 1983,
Physiology and Medicine for your work.
Just to avoid any doubt, our current knowledge about the genomes of
Living beings confirm that genes occupy fixed positions on chromosomes.
Transposable elements are segments of DNA that present
a particular behavior.

In this case, the mutation occurred due to an insertion, but

other types of mutations can modify DNA sequences. You
could you identify other processes that could alter the sequence
of the nucleotides of the DNA molecule?
Let's see if you answered correctly: the sequence of nucleotides of
The DNA of a gene can be altered by:

insertion or addition of one or more pairs of nucleotides;

2. deletion or loss of one or more pairs of nucleotides;
3. substitution of one or more pairs of nucleotides.

144C E D E R J
 Any mutation that occurs within a given gene
it will produce a new allele of this gene. Genes can have multiple
alleles, such as the case of the gene that codes for the protein of the molecule of
hemoglobin (Figure 8.5).

Figure 8.5: Examples of amino acid sequences in the chainβ of hemoglobin.

Each chain shows the exchange of an amino acid when compared to the chainβA
what composes Hemoglobin A (HbA - normal). All the presented examples
result from the substitution of a pair of bases in the nucleotide sequence of the gene
that codes for the proteinβ. Thus, each of these mutations gave rise to a new
allele of the gene for the chainβ.
In this gene, the most well-known mutation is the one that causes sickle cell anemia.
in the human species. If we compare the DNA of the allele that encodes the chain
beta normal (βA) and the allele that codes for the mutant chain (βSthat causes sickle cell disease,
we will verify that the difference between them boils down to the substitution of a single
pair of nucleotides, among the 438 pairs that encode this polypeptide chain. In
DNA region that encodes the sixth amino acid, the triplet of bases is CTC in the allele.
normal and CAC in the sickle allele. Check the genetic code table that is
the substitution of thymine by adenine causes the substitution of a glutamic acid by
a valine in the amino acid sequence of the protein.

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Basic Genetics | From gene to phenotype

THE EFFECTS OF MUTATIONS ON PROTEIN FUNCTION

The DNA modification (mutation) results in variation in phenotype.

For example, a substitution of a nucleotide may occur that does not result in
change sequence of amino acids of the protein to be coded. Give another
look at the genetic code table and you will see that the code is degenerate, or
Thus, there is more than one set of three bases that codes for the same amino acid.

a) without mutation b) amino acid exchange

exchange of a base

DNA

Figure 8.6: Types mRNA CUU CCU

of mutation according to- Lion Pro
make the change that
cause in the function of conformation and new conformation
protein. normal activities of protein and loss
of the protein. due to the activity
to the change of
amino acids.

silent mutation nonsense mutation

exchange of a base exchange of a base

CUU CUA CUU CUG UAC UAA or UAG

Lion or Tyr Film
Lion Leu Leu
incomplete protein
conformation and
normal activities
from the protein. loss of activity

e) change of reading frame

addition of bases

change of conformation

loss of activity

146C E D E R J
Another possibility is when, even with the substitution of one or
but amino acids, the protein continues to perform perfectly the
your function. The change of aa can occur, for example, in a region
of the protein that is not essential for its activity. Figure 8.6
presentsthepossibilitiesofalteringthefunctionofaproteinwhen
your corresponding gene undergoes mutation.

O geneticista Hermann Muller propôs um sistema de classificação

for the mutant alleles according to the changes they cause in relation to HERMANN
function performed by the normal allele of the gene. According to the system of MULLER

classification proposed by MULLER,the alleles can be:

Hypomorphic, when the mutation causes a decrease in

function of the gene in relation to the normal allele.

2. Amorphous, when the mutation, although it maintains the capacity

Amutation in the allele that produces RNAor protein causes loss of function.

do gene.
3. Nulls, when the mutation eliminates the allele's ability to
production of the RNA or protein encoded by the gene. Everything

null allele is an amorphic allele, but not all amorphic alleles are
a null allele. To know if an amorphic allele is also
a null allele, we need to perform a test capable of detecting it
physical presence of the gene product, that is, the protein or
do RNA.
4. Hypermorphics, when the mutation causes an increase in function
of gene in relation to its normal allele.
5. Neomorphics, when the mutation produces a new function.
Antimorphics, when the mutation produces an antagonistic function
to the function performed by the original allele.

The first three classes include alleles where there is a loss of function,
while in the last three the mutation creates alleles that exhibit gain of
function in relation to the original allele. An allele classified as amorphic
it can or cannot be a null allele.
Don't worry about memorizing these names, but rather about understanding.

what each of the classes presented represents in terms of the

alterations in the function of the corresponding proteins.

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Basic Genetics| From gene to phenotype

THE DOMINANCE RELATIONS BETWEEN ALLELES

OF THE SAME GENE

Dominance is the relationship between two alleles of the same gene, which is

defined by the phenotype of heterozygous individuals for these two alleles.

In the study conducted by Mendel, for the seven characters analyzed,
the alleles exhibited a relationship of complete dominance. In other words, the
the phenotype of heterozygous plants was identical to that of homozygous ones
for one of the alleles.
There are cases where the phenotype of the heterozygote is intermediate in

In relation to the two homozygotes, we say that there is a dominance.

incomplete. An example of incomplete dominance is the case of the gene that
determines the color of the flower in Mirabilis jalapa. One of the known alleles

of this gene (A1red color is conditioned by the flower and the other allele (A2), a heart
white. Heterozygous individuals (A1A2) have pink flowers.
One point that generally causes confusion is the difference between the

concepts of incomplete dominance ecodominance. Let's see if

we managed to solve this. We say that there is codominance when
we are able to perceive, in the heterozygote, the phenotype expressed by the
two alleles in question. Most examples of codominance
it occurs when we are analyzing characteristics whose phenotype is
directly related to the identification of the encoded protein
by the gene. Is it still not clear?

Let's go to the classic example, blood groups. The system

ABO blood type in humans is controlled by a gene (GeneI),
which has several alleles. Among these alleles, there is allele I.A, that produces
the specific antigen A and the allele IBthat produces the specific antigen
B. The homozygotes IAIAonly produce type A proteins, the phenotype
of these individuals for the ABO system is blood group A. Similarly
forms the homozygotes IBIBare from blood group B. The heterozygotes
IAIBwe produce both types of proteins, but that is not all, we are
able to identify these products separately, that is why we say
that these alleles exhibit codominance. The heterozygotes IAIBare
of blood group AB. In the case of the gene that encodes the antigens of
ABO system, it is customary to identify the difference between the allele product.

IA(antigen A) and the allele IB(antigen B) through antigen reactions-

antibody, an alternative to the electrophoresis technique.

148C E D E R J
 There is another case in which heterozygous individuals have phenotype
more extreme than both homozygotes. In this case, we say that the
the relationship between the alleles is desobdominance. In Arabidopsis thaliana,

a plant widely used as an experimental model in Genetics,

it was observed that there is a gene whose mutant allele in homozygosis produces

the dwarf plant phenotype. But the heterozygous plants carrying

a normal allele (An) and a mutant allele (an) have a size
greater than the homozygous (AnAn).

ALLELES OF THE SAME GENE CAN PRESENT

DIFFERENT DOMINANCE RELATIONSHIPS

Let's look at an example of how alleles of the same gene can

introduce different dominance relationships.
One of the genes that determines eye color in Drosophila
melanogaster is located on the X chromosome and is called gene
white. The normal or wild allele (w+) this gene encodes a protein
that is related to the deposition of pigments in the eyes of the Drosophilas.
Normal drosophilas have dark red eyes, resulting from
deposition of two pigments, the red pigment and the brown pigment.
There are, however, mutant alleles of this gene that cause the appearance-
a study of different phenotypes related to variation in eye color.
Among these alleles are the white allele (w) and the white-apricot allele (w.a).
The protein encoded by the allele completely loses its function and
is not able to deposit the pigments. The coded protein
by the authoritiesa, although it is still capable of depositing the pigments, it has

its reduced function. Result: the homozygous individuals for the allele
they have white eyes, for they are incapable of depositing any
amount of pigment in the eyes. Homozygous individuals for the
alelowathey have orange-colored eyes.
If we use Muller's classification, we will say that the allele is
amorphic, as it is not able to perform the function of the normal allele of
eye pigmentation, and the alelowais classified as hypomorphic,
then, the function of the eye pigment gene, although retained,
is reduced.

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Basic Genetics | From gene to phenotype

Regarding dominance relationships, the wild allele (w+has

complete dominance regarding these two genes; heterozygous females
ticasw+wow+wathey have dark red eyes. However,
the alelowait exhibits incomplete dominance in relation to the allele, because

femalesathey present eyes with a lighter shade of orange than

homozygous femalesawa.
An allele that encodes a defective protein is recessive when,
in heterozygosity with the normal allele, the latter is still able to provide
the adequate amount of protein to meet the needs of the cell
(haplo-sufficiency). If this is not the case, there is haplo-insufficiency.
normal allele. In our example, the normal allele (w+) is capable of supplying
the requirements for eye color to be normal, even when in
heterozygous with the defective alleles; therefore, there is a haplo-sufficiency
of this allele.

!
Just to remind, male Drosophila are XY; because they have only one
X chromosome, the use of the terms homozygous or heterozygous does not apply.
to refer to the genotype of genes located on its chromosome
sexual X. We use the term hemizygous in this case, that is, the males.
they are homozygous for this or that allele. The same observation applies
for any species that presents a similar determination system
sex chromosomal.

150C E D E R J
 How can we directly identify the protein encoded by the gene?

The technique known as electrophoresis (from the Greek phoresis, migration) allows separation.
molecules with different charges and/or molecular weights. To do this, one must place the
samples to be tested at one end of a gel and apply to this gel a
electric current. The proteins will migrate faster or slower depending on their molecular weight.
structure and its electric charge, which depend on the sequence of amino acids. After the migration

In this way, the position of each molecule can be identified, indicating possible differences or
similarities between the samples. The electrophoresis technique is also used to separate
DNA and RNA molecules.

Figure 8.7: Schematic representation of an electrophoresis gel where samples from individuals with diffe-
genotypes were analyzed. Note that homozygous individuals form only one band
in electrophoretic running, while the heterozygote forms two. This occurs because in homozygotes the
two alleles form identical proteins. Heterozygotes, on the other hand, have two different alleles and, consequently,
They can form proteins with differences in their amino acid sequences.

SOME EXAMPLES OF MOLECULAR BASES OF

SOME GENETIC DISEASES IN THE HUMAN SPECIES

Cystic fibrosis

Cystic fibrosis (CF) or mucoviscidosis is a disease

daily where a defective allele of a single gene is responsible for
dysfunctions in various organs of the body, such as lungs, liver,
pancreas, intestines and reproductive tract. The main cause of these dis-
functions is the obstruction of ducts in various organs by secretions of
greatly increased viscosity. Individuals affected by this disease
they are characterized by having a high concentration of salts in
sisters, in general, die suffocated by the thick mucus that obstructs their
airways.

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Basic Genetics | From gene to phenotype

FC is an autosomal recessive disease. This means that the

the gene whose mutant allele causes this disease is located on a cro-
autosomal recessive, and for a person to be affected, both of their
copies of the gene must be defective. The gene whose mutation causes CF
(GeneCFTR) is located on the long arm of chromosome 7. A
person who carries the normal allele of the gene on one of their chromosomes and

A defective allele on the homologous chromosome does not present the disease.

In this case, as in the examples of the gene for seed texture

pea and the color of the eyes of the drosophila, we say that there is a haplo-sufficient

meaning, that is, the presence of a single normal allele produces the amount
sufficient protein to provide normal cell function and,
consequently, the normal phenotype of the individual.
But what is the primary cause of cystic fibrosis?
As we saw, CF is a monogenic disease. This indicates that the
The primary cause must be a defect or lack of the functions of a protein.
In this case, the disease is primarily caused by the inactivation of a
Figure 8.8: Location of
gene whose mutation causes protein that controls the passage of ions through the cell membrane
cysticfibrosis,inthe
long arm of the chromosome in the secretory tissues. The loss of the protein channel through which
[Link] three pairs
ions cause an imbalance in the concentrations of Na+ Cl-, leading to
graymarkeddebase
resultanaremoçãodoami- production of very thick mucus and obstruction of the ducts in the diver-
no phenylalanine in
corresponding protein. these organs.
Checkthecodetable
go genetic and verify the More than have been detected
amino acid sequence
in the normal protein and in the
1000 alleles with different mutations
mutant. that cause the loss of function of this
protein. However, most of the indi-
Chromosome 7 Sequence of Amino acids
of the protein
affectedindividualsarecarriersoftheallele
nucleotides
CFTR I am
sequence mutant named∆F508. A dife-
A difference between this allele and the normal allele
Isoleucine 506
T
C consists of a deletion of 3 pairs of
bases. The loss of these nucleotides cor-
A
T Isoleucine 507
responds to the production of a protein
C
comparative amino acid phenylalanine
T
T Phenylalanine 508 in 508th place (Figure 8.8).
T

G
Gene CFTR G Glycine 509 Deletion in
C many patients
with fibrosis
cystic
G
T Valina 510
T

152C E D E R J
Tay-Sachs Disease

The homozygous children for the mutant allele that causes the disease
of Tay-Sachs are normal at birth, but after a few months become
are hypersensitive to noises and develop red spots on the retina
of the eye. Between six months and a year after birth, they begin to
to suffer a progressive neurological degeneration that quickly leads
to mental retardation, blindness, deafness, and general loss of control of functions

corporeal. Death, in general, occurs between three and four years of age.
In most global populations, the allele that causes the disease of
Tay-Sachs is rare; however, among the Ashkenazi Jewish population.
from Central Europe, the number of children born with the disease is
about 1 in 3,600 is the number of heterozygous carrier adults
the mutant allele is about 1 in 30.
The mutation that causes Tay-Sachs disease is in the HEXA gene.
which encodes the enzyme hexosaminidase A. This enzyme acts by cleaving the
ganglioside G lipid complexM2in a smaller ganglioside (GM3) e
in N-acetyl-D-galactosamine.

GeneHEXAnormal

code to

Enzymatic protein hexosaminidase A

catalyzes the reaction

GM2 ganglioside ----------------- GM3 ganglioside + N-acetyl-D-galactosamine

The function of ganglioside GM2is to coat the nerve cells,

isolating them from events that occur in neighboring cells and accelerating
the transmission of nerve impulses. In the absence of the enzyme that it
degrade, there is an excess of GM2that accumulates in the cell.
The accumulation of complex lipids in the nerve cell blocks its
action, leading to the deterioration of the nervous system and paralysis.

CEDERJ 153
Basic Genetics | From gene to phenotype

Sickle cell anemia

Hemoglobin is a protein responsible for transport of

oxygen gas in our body. It typically consists of two pairs.
different polypeptide chains. In normal adult hemoglobin
(Hemoglobin A - HbA), these chains are designatedα (alpha) andβ (beta).
The four chains are organized into a globular structure with
the formulaαAβ2Awhere
2
the index indicates
A that the polypeptide chains
α eβ are of normal type and the index2, which are represented in dose
double (Figure 8.9). The chainα is encoded by a gene located on
chromosome 16, while the gene that encodes the chainβ it's in the cro-
mossomo 11.

Figure 8.9: The four levels of organization of human hemoglobin - primary, secondary, tertiary structure
the quaternary structure of the protein, with emphasis on the chainβ.

154C E D E R J
 Sickle cell anemia (from the Latin falcis, sickle) or sickle cell disease (from English)

sickle cell disease is a hereditary disease, characterized by a severe

anemia, often fatal. As we have seen, this type of anemia is
caused by a mutation in the beta chain of hemoglobin that results in
change of a glutamic acid to a valine at position 6. This chain
mutant is calledβSand the hemoglobin that it has is Hemoglobin
S (HbS), whose formula isαAβ2S2(Table 8.1). Altered hemoglobins
tend to aggregate, forming rod-shaped masses that distort
the red blood cells into a sickle shape. These deformed red blood cells do not

they move easily through the fine blood capillaries, causing damage
to various tissues, mainly bones and kidneys. In addition, the red blood cells
deformed ones break easily.

Table8.1:Thethreepossiblegenotypesregardingthetwoalleles,βAeβS, their respective phenotypes and the relationships of

dominance among these alleles. Note that the concept of dominance is relative, depending on what we are
considering as the phenotype.

Phenotypeintermsofshape
Phenotyperegardingshape the hemocytes in condition-
Phenotype regarding composition the red blood cells in conditions-
Genotype
themoleculesofhemoglobin lowconcentrationactions
normaloxygenconditions
oxygenation

αAβ2 A(HbA)
βAβA 2 normal form normal form

αAβ2 A, 2αAβS2(HbA
2
and HbS) deformation
βAβS normal form
eαAβ2Aβs intermediate

accented form of accentuated form

βS βS αAβ2 S2(HbS) of the sickle
scythe

Relationship of
dominance
dominance codominance complete dominance
incomplete
amongthealeles

With the classes we have seen so far, we hope you feel

familiar with the organization of the genome and with the processes of
expression and transmission of biological inheritance. We also hope
that you can establish the relationships between Mendel's Laws and the
cellular processes.

C E D E R J 155
Basic Genetics | From gene to phenotype

INFORMATION ABOUT THE NEXT CLASS

Our next class will be an introduction to the methodology of genetic analysis.

human species.

SUMMARY

Genes are segments of the DNA molecule responsible for storing and
transmit genetic information. DNA serves as a template for the manufacture of
an RNA transcription, which may contain information for the synthesis of a protein
Proteins can have structural or enzymatic functions, being these
determined by the amino acid sequence of the protein.

The nucleotide sequence of DNA can be altered (mutation) by: insertion,

deletion or substitution of one or more pairs of nucleotides. The mutations in
DNA can cause modifications in the amino acid sequence of the protein
corresponding with loss or modification of its function. However, not all
variation in DNA results in variation in phenotype. Any mutation that occurs
within a certain gene will produce a new allele of this gene.

We call dominance the relationship between two alleles of the same gene that
is defined by the phenotype of heterozygous individuals for these two alleles.
According to the dominance relationships, alleles can exhibit: dominance
complete, incomplete dominance, codominance or overdominance.

An allele that encodes a defective protein is recessive when, in

heterozygous with the normal allele, the latter is capable of providing the amount
sufficient protein to meet the needs of the cell (haplo-sufficiency).
The concept of dominance is relative, depending on what we are considering.
as the phenotype.

156C E D E R J
 EXERCISES

In the last class, you started building a glossary. Continue this.

Activity including now the **bold** words in the text of this lesson.

2. Fill in the blanks in the sentences using the term below more
appropriate.

allele heterozygous diploid

(b) at the place homozygous haploid

(c) gene dominance

(d) mutation h) codominance

2.1. ( can be defined as the portion of the chromosome (a segment of the

moleculeofheredity)thatproducesadetectableeffectontheindividual.

A hereditary change in a characteristic is called ).

2.3. Each of the detectable forms of a ( ) is called ( ).

2.4. The position that a certain ( ) occupies on the chromosome is its ( ).

2.5. The zygote, and consequently the individual, resulting from the union of gametes
carriers of the same type of allele is called ( ).

2.6. The zygote, and consequently the individual, resulting from the union of gametes
carriers of different alleles of the same gene is called ).

2.7. The phenomenon of one allele of a gene masking the effect of another allele
same gene is called ( ).

2.8. In the crossing between an individual with a dominant hereditary trait

and another with the recessive character, all descendants presented the
dominant character. It can be said, therefore, that, very likely,
the dominant parental type is ( ).

2.9. In a cross between an individual with a hereditary trait

dominant and another with the recessive character, descendants were produced
with the dominant trait and descendants with the recessive trait. This
the result allows us to conclude that the dominant parental type is ( ).

An individual who has only one allele of each in their cells.

gene is ( ).

2.11. An individual who presents in their cells a pair of alleles of each

gene is ( ).

C E D E R J 157
Basic Genetics | From gene to phenotype

In sweet peas, the synthesis of the purple pigment in the petals is controlled by
two genes, BeD. The normal allele of gene B, allele B1, codes for enzyme B that
participates in the first stage of the metabolic pathway for the synthesis of the purple pigment.

The aleloD1do gene codes for the enzyme D, which participates in the second stage of the pathway.

geneB alleleB1 allele D1 gene D

codify code

Enzyme B (functional) Enzyme D (functional)

transform transform

substância inicial (branca) ---------- substância intermediária (azul) ---------- pigmento final (púrpura)

What color do you expect the petal of a homozygous plant to have?

a recessive mutation that prevents the first reaction?

What color do you expect the petal of a homozygous plant to have?

a recessive mutation that prevents the second reaction?

c. What is the genotype of the plants mentioned in a and b, according to the two genes in
Question? Choose the symbol for the recessive mutant alleles.

4. Imagine that, when dosing the enzyme encoded by gene E, in Drosophila

melanogaster, a researcher observed the following results, depending
of the individuals' genotype:

Wild-type homozygotes (normal) = 20 units of the enzyme;

Homozygous for a mutant allele = 0 units of the enzyme;

Heterozygotes = 10 units of the enzyme.

The researcher also observed that the heterozygous flies had the same
phenotype of the mutant homozygotes. Interpret these results.

158C E D E R J
5. Normally, the growth hormone (thyroxine) is produced from the
following reaction:

(enzyme)

Tirosina -------------------- Tiroxina

If the enzyme that catalyzes this reaction is deficient, the individual

begins to show a disease known as cretinism, a syndrome
rare condition that consists of slow growth, enlargement of the thyroid, and retardation

mental. Sabendo que o alelo normal que codifica a enzima em questão é

haplo-sufficient, you expect that this disease will be inherited with a phenotype

recessive or dominant?

ACTIVITY 1

In addition to the ABO blood group system, there are other blood group systems.
in the human species. Do some research on the genetics of fur determination.
less three of these systems, including the ABO system. For each system, look for
discover the chromosomal position of the gene, the number of alleles already identified, the

relationship of dominance between the alleles and, if possible, the molecular difference between them

alleles and how these genes work. Send your research to the tutor by the due date.
indicated in the student guide. This and other future research can be done through
from the material available at the hub, in other libraries, and also on the Internet.

ACTIVITY 2

Huntington's disease (HD) is a monogenic disease characterized by

due to the degeneration of nerve cells. Unlike cystic fibrosis, DH has
autosomal dominant inheritance. Thus, only one copy of the gene needs to contain the allele.

mutant for the individual to present the disease. Do some research and look
obtain information about this disease, especially regarding the bases
molecular causes.

C E D E R J 159
Genética Básica| Do gene ao fenótipo

APPENDIX

Table 8.2: The genetic code. Each triplet of nucleotides (or codons) refers
it is the nucleotide sequence of the mRNA and carries the information for the
the respective amino acid is added to the protein being constructed. Marked in
gray are the initiation (AUG) and termination (UAA, UAG, and UGA) codons of translation
of any protein. The name of each amino acid is abbreviated as follows
way: phenylalanine (Phe), leucine (Leu), isoleucine (Ile), methionine (Met), valine
(Val), serina (Ser), prolina (Pro), treonina (Thr), alanina (Ala), tirosina (Tyr), histidina
(His), glutamine (Gln), asparagine (Asn), lysine (Lys), aspartic acid (Asp), acid
glutamic (Glu), cysteine (Cys), tryptophan (Trp), arginine (Arg), glycine (Gly).

160C E D E R J
 Introduction to Human Genetics:
analysis of characteristics
monogenic 9
By the end of this lesson, you should be able to:
Identify the main modes of transmission
two genes in human families.
Build pedigrees.
• Establish the criteria used to
recognize the different inheritance patterns
monogenic through pedigrees.
Apply the laws of probability for calculation of
risks associated with genetic issues.

Prerequisites
Record the fundamentals
of probability: laws of
addition and multiplication and
also distribution
binomial - probabilities
binomial.
Basic Genetics | Introduction to Human Genetics: analysis of monogenic traits

As soon as the laws governing the transmission of biological inheritance

discoveries were made, efforts were made to extend genetic studies to the species
human. However, there are some peculiarities in the study of patterns.
of inheritance in humans resulting from the inadequacy of our
species as experimental material. Unlike species such as the
P O LY M O F I S M peas or fruit flies, the human species presents: small number
GENETIC
of individuals in the offspring; long generation time; and impossibility of
The concept of
polymorphism manage mating. Thus, although the laws governing transmission
genetic refers to
if to the frequency that inheritance in peas or humans may be similar, the methods
two alleles of a used for your studies are different. The study of inheritance of
determined gene
in a population. Characters in the human species constitutes a special branch of Genetics.
It is said that a
gene presents known as Human Genetics.
polymorphism Human Genetics has become an area of particular interest
when this has
at least two two scientists for their importance in clinical practice, through their
normal alleles in
population, having the role in the etiology (origin) of various disorders. Many human genes
the rarest ale
were identified through a clinically significant disorder
higher frequency
a 1%. caused by a mutant allele of this gene. Virtually any disease
In the human species, is the result of the combined action of genes and the environment, although the role
for example, the
characteristic shape the relative of each of these factors may vary. The main disorders
of the lobe (or wolf)
from the ear (loose or caused totally or partially by genetic factors can be of three
(pressure) is determined
types: monogenic, chromosomal, or multifactorial.
for a gene that
has at least In this lesson we will focus on the study of the characteristics
two alleles, being the
allele that determines with monogenic inheritance, analyzing examples related to both
the loose state
dominant over disturbances regardingGENETIC POLYMORPHISMSin the human species.
what determines the
state imprisoned. These Multifactorial characteristics, that is, conditioned by the interaction of
two alleles are in several genes and their interaction with the environment will be studied in future classes,
high frequency in
population, what as well as some of the disorders caused by the variation in number or
it can be observed
due to the high frequency structure of human chromosomes.
of individuals with
In studies of the determination of the pattern of inheritance of
each of the types of
phenotypes. We say
human characteristics cannot perform experimental crosses.
so that the gene
what conditions The analyses are made based on the survey of the family history, what
shape of the lobe of
ear is polymorphic It allows assessing whether a certain characteristic is hereditary or not.
and also that
this characteristic
and how it is inherited. This survey is conducted based on a
it is polymorphic graphic representation called a pedigree (from the Latin hereditariu),
in the population
human. Many of the also known as genealogy, family tree or pedigree.
features in
various species are
polymorphic.

162C E D E R J
THE CONSTRUCTION OF HEREDOGRAMS

In the construction of pedigrees, we use symbols for the

individuals of a family and their kinship relations. Figure 9.1
presents the symbolism used in the construction of pedigrees and the Figure
9.2 presents the example of a pedigree.

Figure 9.1: Symbols used in pedigree diagrams.

C E D E R J 163
Basic Genetics | Introduction to Human Genetics: Analysis of Monogenic Traits

Figure 9.2: Family pedigree.

The bold symbols represent individuals affected by
a genetic anomaly

Activity

E x p re s s i v e n e s s You should build your family's heredogram regarding

VA R I A B L E
characteristic shape of the earlobe. Be strict in its use.
It is said of the allele that
two symbols, include as many individuals as possible and look for
does not manifest
exactly from determine your genotypes.
same form in
all individuals By doing this activity, you will see that for some individuals the
that they possess.
classification between free or imprisoned is very easy to make, but for others
not so [Link] thing that eventually happens is the appearance
of cases that cannot be explained by the phenotype of the parents.
P E N E T R AT I O N
INCOMPLETE These cases can be explained by the fact that gene action is more
It is said of the allele that,
affected by biological or physical factors of the environment, which can
even being
present, can or result in theVARIABLE EXPRESSIONtwo alleles of a gene or in itsPENETRATION
not to express oneself
in the individual INCOMPLETEWe will return to these concepts in Lesson 11 and will also see
whose genotype
how to analyze genealogies that present these and other phenomena. In
I should express it
phenotypically. just know that you should not be alarmed if your pedigree
present some unexpected result.

164C E D E R J
ANALYSIS OF HEREDOGRAMS AND PATTERNS
ON MONOGENIC INHERITANCE

In order to establish the transmission standard of a characteristic,

the first step is the construction of the pedigree. The analysis of the pattern

presented by the pedigree allows us to determine the most pattern

likely transmission of the inheritance for the characteristic in question.
Many times we are inclined to do this through trial.
and error, considering each of the possible inheritance patterns
(autosomal dominant, autosomal recessive, X-linked dominant,
linked to the recessive X) and, for each of the possibilities, trying
adjust the genotypes of the family members. This is undoubtedly not
the best, not the most elegant way to analyze a pedigree.
So, how to proceed? Let's look at the pedigrees as
a whole and look for patterns that indicate the type of inheritance more
likely. In Table 9.1 are some tips about the different patterns
of inheritance that facilitate its recognition.

Framework 9.1: Criteria for assessing the pattern of inheritance of monogenic traits in pedigrees

Autosomal recessive Autosomal dominant

Approximately equal frequencies of Approximately equal frequencies of
males and affected females. affected males and females.
Almost always the trait skips generations. 2. In general, the trait appears in all
3. The trait can appear in siblings without the generations.
be present in your country. At least one of the parents of a
affected individual is affected

X-linked recessive Linked to the dominant X

The trait is more common in men than Normally, all the daughters of a man
in women. affected will be affected.
2. There is no transmission from father to son. 2. There is no transmission from parent to child.
All the daughters of an affected man are
carriers of the mutant allele.

C E D E R J 165
Basic Genetics | Introduction to Human Genetics: analysis of monogenic traits

Now,basedontheexpositioninTable9.1,youcantrytodetermine
thetypeofinheritancemostlikelyforthetraitspresentedinboldinthe
[Link]
[Link].

Figure 9.3: Pedigrees showing the inheritance of various traits.

166C E D E R J
APPLICATION OF PROBABILITY CALCULATIONS
TO HUMAN GENETICS

In human families, the number of children produced by a couple

it is typically small. Consequently, the phenotypic proportions in
generally deviate significantly from their theoretical expectations.
Let's take a hypothetical example. Suppose a couple where
both spouses are heterozygous for a gene that has two
alleles, Fef, with allele F being dominant over allele fe conditioning the
normal phenotype. Individuals who present the homozygous alelofim
are affected by a certain disease.
Our knowledge about the segregation of alleles during the
the formation of gametes allows us to say that each of the members
this couple will form gametes carrying the recessive allele
and carrying the dominant allele F. As fertilization occurs at
perhaps, we could obtain the zygotes resulting from fertilization of
all the gametes produced by this couple we would observe that: would be
homozygous FF is normal; would be heterozygous Ff, also normal
It would be a heterozygous affected.

Table9.1:ExpectedprobabilitiesintheoffspringofaheterozygouscoupleforgeneF.

Mother's gametes
1/2 F 1/2 f
Gametes of the Father

1/2 F 1/4 FF normal 1/4 Ff normal

1/2 f 1/4 fF normal 1/4 ff afetado

Likewise, if the couple has four children we expect

that 3 are normal and 1 is affected, right? No, wrong. There are five.
distinct possibilities:
1) 4 normals;
2 normal and 1 affected;
3) 2 normals and 2 affected;
1 normal and 3 affected;
5) 4 affected.

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Basic Genetics | Introduction to Human Genetics: analysis of monogenic traits

Intuitively, the second outcome seems to be the most likely.

for it is in accordance with the Mendelian ratio 3:1. But this is not the
the correct way to proceed with this analysis. When we analyze this issue,
we should treat each birth as an independent event for the
calculation of probability. That is, when we consider a birth,
the probability of the child in question being normal is . If
considering the four births, the probability of each child
being normal is from , but the probability of all four children being
normal will be × × × = ( )4= 81/256 (remember the rule of
multiplication). Similarly, the probability of a child being
the affected will be and the probability of the four children being affected
will be ( ) = 1/256.
4

So far so good, but what is the probability of the couple having

one of the four children affected, regardless of their sex?
Once again we have more than one possibility:
the first child to be born to be the affected one and the other three to be
normals (ANNN);
the second child to be born is the affected one and the other three are
normals (NANN);
the third child born to be the affected one and the other three to be
normals (NNAN);
the fourth child to be born is the affected one and the other three are
normals (NNNA).

Let's then calculate the probability for the possibility

1 (P(ANNN)), that is, the first child being affected and the second
not being affected and the third not being affected and the fourth not being affected:

(= probability of the first being affected) × (= probability of the

second normal) × (= probability that the third is normal) ×
(= the probability of the fourth being normal) = 27/256. In the same way,
we can calculate the probabilities for the other three possibilities
(P(NANN), P(NNAN), P(NNNA)). In all cases, the probability
it will be the same, 27/256. Finally, the probability of one of the children
of the couple being affected by the disease, regardless of whether it is the first one, or

second, or third or fourth equals the sum of the probabilities

for each of the possibilities, that is: 27/256 + 27/256 + 27/256 +
27/256 = 4 × (27/256) = 108/256 (addition rule).
Now it's your turn. Calculate the probability of the couple having only
one of the four normal children.

168C E D E R J
 The result would be: P(NAAA) + P(ANAA) + P(AANA) + P(AAAN) =
4 × (3/256) = 12/256. In Table 9.2 you can check the probabilities.
associated with all the possibilities of phenotype for the four children of the
couple in the case in question.

Table 9.2: Probabilities associated with the phenotype of the 4 children of a heterozygous couple for a gene
autosomal whose recessive allele causes a certain disease.

Normals Affected Probability

4 0 1 × ( ) × ( ) × ( ) × ( ) = 81/256

3 1 4 × ( ) × ( ) × ( ) × ( ) = 108/256

2 2 6 × ( ) × ( ) × ( ) × ( ) = 54/256

1 3 4 × ( ) × ( ) × ( ) × ( ) = 12/256

0 4 1 × ( ) × ( ) × ( ) × ( ) = 1/256

Does all this talk remind you of the Probabi-

Binomial probabilities? That's it, we can obtain a generalization for the
estimation of the probabilities associated with the outcome of crossings
genetics applying the formula of the binomial distribution. This can be
done whenever the offspring from the crosses segregate into two classes
different, for example, male or female, normal or affected, dominant
or recessive.
The formula to calculate the binomial probability that x
individuals of the offspring fall into one of the classes is:

[n! / (x! y!)] pxqy

Formula 9.1

where:
n= total number of offspring;
x = number of offspring individuals belonging to the first of two
possible classes;
y = number of offspring individuals that belong to the second of two
possible classes;
p = probability of each individual in the offspring belonging to the first

of the two classes;

q = probability of each individual in the offspring belonging to the second

of the two classes.

C E D E R J 169
Basic Genetics | Introduction to Human Genetics: analysis of monogenic traits

There's no need to be scared. With an example, everything becomes easier.

Returning to the couple where both were heterozygous for the gene
ehsontaeuhosm
ic'lL
btrufalcteiuhlroefnotm
bsiladii
probability that, having 4 children, one of them is affected. In this case,
we can use the binomial probability because in the offspring we have two classes
possible, the first, to be normal; and the second, to be affected. We then have
que: n = 4; x = 3; y = 1; p = ; q = .
Applying these values to Formula 9.1 we obtain:

[4! / (3! 1!)] ( )3( )1=

[ (4×3×2×1) / (3×2×1×1) ] 27/64 × 1/4 =
4 × 27/256 = 108/256,
value that matches what we estimated earlier.

Let's see one more example to ensure that the subject is

Understood. Consider that a couple intends to have three children and wants to know

What is the probability that everyone is male? We have two

possible classes for the offspring, the first being male; the
second, to be of the female sex. We applied the formula with the values
de n = 3; x = 3; y = 0; p = ;q= . Thus, [3! / (3! 0!)] ( )3( )0=
27/27 × 1/8 = 1/8, remembering that 0! = 1 and that any number raised
zero is also equal to 1. The answer, then, is that the couple has a
a chance of 1/8 (or 0.125 or 12.5%) that, having three children, all three will be

male.
Another application of the laws of probability in Genetics
Human occurs when future parents wish to know if their children
they are at risk of inheriting a certain condition, especially
if other family members are affected. The risk assessment
requires a good knowledge of Genetics, combined with familiarity with
probabilities and statistics. This analysis begins with the construction of the
family genealogy, aiming to determine the most likely pattern of
inheritance and, when possible, the genotype of the parents.

Now you will participate in genetic counseling regarding the issue

Next. Imperfect amelogenesis due to hypomaturation is a disorder.
of the enamel of the teeth, where they become less resistant and their
coloration ranges from milk-white to a light brown that is somewhat transparent.

170C E D E R J
The enamel is brittle, breaking off in small fragments. Three
couples from the same family sought counseling services
genetic to know the risk of having children affected by this anomaly,
since there are cases in the family. Figure 9.4 shows the pedigree of the
family in question. The people who requested the information were the
couple III-3 and III-4 and the couple II-7 and II-8. The third couple is formed by the
individuals IV-1 and IV-2, who intend to get married, but are apprehensive about
the likelihood of having children with the anomaly. What would you say to each
one of these couples?

Figure 9.4: Pedigree of a family with amelogenesis imperfecta due to hypomaturation.

The analysis of the pedigree allows us to conclude that this type of

imperfect amelogenesis shows an autosomal inheritance pattern

recessive. In addition to the characteristics already listed in Table 9.1, it is observed

even if the couple III-3 and III-4 are cousins. What does that have to do with it?

Most of the alleles of autosomal recessive disorders

is present in carriers (heterozygotes) and not in homozygotes.
They can be passed down in families for numerous generations without
never appear in the homozygous form. In fact, it is believed that all
people have at least some alleles of autosomal disorders
recessive, which in homozygosity could be harmful or even lethal.
The presence of these recessive alleles is revealed when the carrier
marry someone who has the same mutation, or another mutation

C E D E R J 171
 Basic Genetics | Introduction to Human Genetics: analysis of monogenic traits

tion in the same place, and both deleterious alleles are inherited by some
of their children. The chance of this happening is greatly increased if the parents
related forms, as in the same family several individuals may
to be carriers of the same mutant allele that is passed along the
generations. The consanguinity of the parents of a patient with disorder-
genetic bio is strong evidence (although it does not prove) in favor of the
autosomal recessive inheritance.
Returning to the analysis of the pedigree, individuals III-3 and III-
4 are heterozygous (Aa) for the allele in question, which indicates a
probability of (25%) that your next child,
! Regardless of gender, be affected by the anomaly.
When we analyze a pedigree of a
we must consider that genetic anomalies In the case of couple II-7 and II-8, the woman (II-8),
the individuals coming from the population, or
that is, the unaffected individuals of the population
being affected, is a recessive homozygote (aa).
who marry someone from the family, are Regarding the man (II-7), he is an individual who does not
homozygous for the normal allele of the gene
in question. This is because, in the case of anomalies belongs to neither of the two lineages where the allele
rarely, the mutant allele is at low frequency
in the population, the chance is very small what causes imperfect amelogenesis is segregating.
of an individual from the general population to be
Logo, the chance of him being a carrier of this allele is equal
carrier of this allele. However, the chance
of an unaffected individual from the family in
the issue of being a carrier of this mutant allele
the chance of any individual in the population, that is,
itwildependontheanalysisofthephenotypeandofthe
very low. We can consider it negligible, being
genotype of your ancestors and, when possible,
from the analysis of its descendants. it is very likely that II-7 is a dominant homozygote
The chance of this couple having an affected child
the anomaly in question is approximately zero. However, all
your children, regardless of sex, will carry the allele a.
In the case of the couple IV-1 and IV-2, the probability calculation is a
a little more complicated, because we do not know if they are or not
carriers of aleloa. We will then have to calculate the probability of
they are carriers. Starting with IV-2, as we already know that he
is not affected, the probability of being a carrier becomes 2/3. This
because, as her sister (IV-3) is affected (aa), we can deduce that
both your mother (III-3) and your father (III-4) are heterozygous (Aa).
Thus, considering the four genotypic possibilities resulting from
a cross between heterozygotes (AA, Aa, Aa, aa), the probability
Of IV-2 being a carrier, there will be 2 chances out of 3 (AA, Aa, Aa, aa), because

Definitely this individual cannot be, since he is not affected.

Let's now calculate the probability of IV-1 having inherited allele A.
paternal grandmother, II.2, is heterozygous and would need to pass the allele to the

individual III-1, father of IV-1. There is a chance of this having occurred.

Having received the aleloa, individual III-1 would need to have gone through the

172C E D E R J
aleloapara IV-1, chance of as well. The probability of these events
the occurrence of event is equal to the product of the probabilities of each of them,

that is, ⊠ x ⊠ = ⊡.
In summary, 2/3 is the chance of IV-2 being heterozygous and 1/4 is the

chance of IV-1 being heterozygous. The chance of the couple having a child
the affected will be equal to the chance of both being heterozygous (= 2/3)× 1/4)
multiplied by the chance of the child receiving from both parents the allele
1/4). That is, 2/3× 1/4× 1/4 = 2/48 = 1/24 (= 0.04 = 4%).

Shall we check the answers to the exercise in Figure 9.3?

A. Autosomal dominant; E. Linked to the dominant X;

B. Linked to the dominant X; evissm
oecsoleA
artu
C. Linked to X recessive; G. Autosomal dominant;
D. Autosomal recessive; H. Linked to X recessive.

It is likely that, in some cases, you have been unsure between two patterns.
possible, but remember that when analyzing a pedigree, we seek to determine the
most likely inheritance pattern.
Look, for example, at the case of pedigree B. Someone might suggest that the inheritance of
trait represented by the bold symbols could be autosomal dominant and not linked
to the dominant X. It is true that both types of inheritance can explain the pedigree B,
but we have to choose the most likely. Note that the man of the first generation presents
the trait is passed on to all of his daughters, but to none of his sons.
children. This is a strong indication that the inheritance pattern in question is likely X-linked.
dominant, as in X-linked inheritance, daughters receive one of their X chromosomes from
father, while the children receive the Y chromosome from the father and never the X chromosome. It is less

it is likely that the pattern presented occurred by pure chance.

INFORMATION ABOUT THE NEXT CLASS

In the next theoretical class, we will see that various factors can alter the pattern of
expected inheritance, including the inactivation of the X chromosome, the age of the individual

and the interactions of the genotype with the environment, for example.

However, our next class will be a practice where we will present strategies.
to solidify the concepts and the conceptual relationships we have seen so far.
Check the Student Guide for the date and time you should go to the
pole and don't forget to bring the results of the activity proposals for this class and
the previous ones for discussion with your colleagues and tutors.

C E D E R J 173
Basic Genetics | Introduction to Human Genetics: Analysis of Monogenic Traits

SUMMARY

Although the laws governing the transmission of inheritance in peas or humans

they may be similar, but the methods used for their studies are different.
The study of the inheritance of traits in the human species constitutes a special branch.

of Genetics known as Human Genetics. In studies of the determination of

human characteristic inheritance pattern we cannot perform crossings
Experimental. The analyses are conducted based on the assessment of the family history.
what allows us to assess whether a particular characteristic is hereditary or not and
how it is inherited. This survey is made based on a representation
graph called heredogram (from the Latin hereditariu), also known as
genealogy, family tree or pedigree. The results of an analysis of
pedigree depends on the distribution of alleles through the gametes passed from
parents for children and allow genetic consultants to determine the probability
of a person inheriting a specific characteristic.

EXERCISES

1. In our pedigrees below, indicate with Y or N if they are compatible.

with the listed inheritance standards.

A B C D E F
Autosomal recessive
Autosomal dominant
X-linked recessive
Linked to dominant X
Linked to Y

174C E D E R J
2. What is the most likely inheritance pattern presented in the pedigrees?
below? Consider that the characteristics in question are genetic diseases that
have very low frequency in the population. Therefore, individuals who come from outside

the family members must be considered homozygous for the normal allele, unless
if there is any contrary evidence.

C E D E R J 175
Basic Genetics | Introduction to Human Genetics: analysis of monogenic traits

3. Catarina is pregnant for the second time. Her first child, Dagoberto, has
cystic fibrosis (CF). Catarina has two brothers, César and Daniel, and a sister, Diva. Daniel
and Diva are single. César is married to a non-related woman, Carolina, and
She has a daughter, Débora. Catarina's parents are Roberto and Eliza. Bárbara, sister of

Eliza is the mother of Catarina's husband. There is no family history of CF.

a) Build the pedigree.

b) What is the inheritance pattern of FC?

c) What is the risk of the next baby having cystic fibrosis?

d) In this pedigree, what are the certain heterozygotes?

4. Analyze the following pedigree:

1 2 3 4

1 2 3 4 5 6 7 8
II

1 2 3 4 5
III

Determine:

a) The pattern of inheriting character.

b) The correct homozygotes.

c) The correct heterozygotes.

d) The probability of couple III-3 and III-4 having three children, one without the
character and two with the character.

5. The lack of dental enamel and color blindness are conditioned anomalies.
by X-linked inheritance genes. A woman with enamel deficiency and vision
normal, who has a colorblind father with normal dental enamel and a mother with deficiency

of enamel and normal vision is married to a color-blind man with dental enamel
normal. This couple has two boys, one with a lack of dental enamel and
color blindness and another color blind person with normal dental enamel. Explain how if

where these boys originated.

176C E D E R J
[Link],theindividualinboldisaffectedbyanautosomaldisease.

rare recessive. Estimate the probability of a child from couple III-1 × III-2 exhibiting
this disease. Note that this pedigree is presented in a simplified form,
suppressing some individuals of the family.

C E D E R J 177
 Practical activity 10
By the end of this lesson, you should be able to:
Relate Mendel's Laws to meiosis.
Analyze the transmission of biological inheritance in
families.

Observation
This class should be held on
pole, under supervision
from your tutor.
Basic Genetics | Practical Activity

INTRODUCTION Cell division is one of the most important topics in high school education, being

essential prerequisite for a deeper understanding not only of the

genetic processes more of a large part of biological phenomena. From this
In this way, the processes of mitosis and meiosis should be studied with a certain degree

of detailing and depth.

You have already seen in the previous lessons that all cells are formed by division.
from pre-existing cells. When a cell divides, the information contained
in your DNA it should already be precisely duplicated and, then, each copy should be
transferred to each daughter cell through a series of complex processes.
Now let's recall some characteristics of these processes (in case of
If in doubt, take a look at the lessons on cell division.
Most of the cell divisions that occur in organisms involve a
process called mitosis, which ensures that each daughter cell receives a copy

of each chromosome and, consequently, of each gene, coming from the

parental cells. However, during sexual reproduction in eukaryotes, two
gametes fuse to form a single cell, called a zygote. Each
gamete must contain only half the number of parental chromosomes,
ensuring the correct maintenance of the number of chromosomes in the zygotes.

For this reason, organisms that undergo sexual reproduction need

of a differentiated type of division, called meiosis, which reduces the number

of chromosomes to half. It is believed that, evolutionarily, meiosis has

developed as a variation of mitosis, allowing the emergence of
sexual reproduction.
Now, with the knowledge obtained in the previous classes, you are ready to
carry out the proposed activity below:

180C E D E R J
 ACTIVITY 1

CHROMOSOMAL THEORY OF INHERITANCE:

RELATING MEIOSIS TO MENDEL'S LAWS

For this activity you will need the following materials:

• Two-colored modeling dough (chromosomes);

• Adhesive labels measuring 2 to 3cm in length (gene region);

• String or thread (chromosomal fibers of the spindle and cell membrane);

• Centrioles (cinetochore and centrioles).

Form a group of no more than four students with your classmates. Each group
You will receive modeling clay sticks in two different colors. Our goal
It will analyze the formation of gametes and fertilization in a couple, considering
two genes for which man is known to be heterozygous and woman
homozygous for the normal allele.

Each group should represent a germ cell from the male testis.
heterozygous during meiosis. To simplify, only the chromosomes
carriers of the genes in question will be represented. That is, of the 22 pairs
of the autosomal chromosomes of a human cell, we will represent the
chromosome 7, which is large and submetacentric, and chromosome 19, which is quite

smaller and metacentric. To assist you, use the illustrated human karyotype in
Figure 10.1.

Each of the homologs in a pair must be modeled in a different color,

representing your maternal or paternal origin. Begin this activity by representing
the chromosomes during the G1 phase of interphase. Note that, although in this phase of the cycle

cellular chromosomes are uncondensed and it is not possible to identify

we are building a model and, for educational purposes, we will represent the
chromosomes already as visible rods in this phase.

C E D E R J 181
Basic Genetics | Practical Activity

Figure 10.1: Assembly of the human karyotype from the

chromosomes of a cell during metaphase of mitosis.

Now place the allele pairs of the two genes (described below) in the
autosomal chromosomes in question. To do this, use the adhesive labels,
representing the alleles.

!
Gene F - gene that conditions cystic fibrosis, a disease characterized by a dysfunction
pancreatic and pulmonary, which usually leads the individual to death in the early decades
of life. It is located on the long arm of chromosome 7. The recessive allele (f) conditions
the disease, and the dominant (F) gives the normal condition.
Gene H - gene that conditions familial hypercholesterolemia, a disease characterized by
elevated levels of cholesterol in the body. It is located on chromosome 19. The allele
dominant (H) conditions the disease, and the recessive (h) gives the normal condition.

The man in question is heterozygous for these two genes (FfHh), that is, he is not
presents cystic fibrosis, but presents familial hypercholesterolemia. It is known that
that your maternal cousin has cystic fibrosis and your father has familial hypercholesterolemia.

Use this information to distribute the alleles on the homologue chromosomes of

each of the pairs.

182C E D E R J
1. Now, think: how many types of gametes should this individual form? Which ones?
Write down your first idea.

__________________________________________________________________________
__________________________________________________________________________
__________________________________________________________________________
_____

It is time to prepare your "cell" to enter division, that is, to duplicate the
chromosomes (S phase of interphase). Then you should simulate the phases of
meiosis, using the chromosomes in question and representing the centrioles
the poles of the cells and the chromosomal fibers of the acromitic spindle. However,
always consider that the exchange between the non-sister chromatids occurs between the

gene considered and the telomere, for the two pairs of homologs. Interrupt
your simulation in metaphase I of meiosis and wait for the tutor to go to you
table to monitor the subsequent phases of the division until the formation of the

gametes. Outline the phases observed on a piece of paper and respond

to the questions:

2. How many types of gametes did the cell you simulated form? Which ones?

__________________________________________________________________________
__________________________________________________________________________
__________________________________________________________________________
_____

Compare your results with those of the other groups. Observe the proportions.
obtained.

3. How do you explain, considering this double-heterozygous individual, that each

one of its cells, when undergoing meiosis, only forms two types of gametes, while
that the individual forms four types of gametes (FH, Fh, fH, fh)?

__________________________________________________________________________
__________________________________________________________________________
__________________________________________________________________________
__________________________________________________________________________
__________________________________________________________________________
_________

C E D E R J 183
Basic Genetics | Practical Activity

Note that a cell that undergoes exchange between the gene in question and the centromere

will form the four types of gametes. However, the frequency of gametic cells
whose exchange occurs precisely under this condition varies according to the distance between the

The gene in question is the centromere. Since it is not the permutation that explains the formation.

of the four types of gametes produced by the double-heterozygous individual in

same proportion (1:1:1:1), what other phenomenon could be responsible for the
formation of the different gametes in this proportion? Do you remember that, during
In anaphase I, the chromosomes of the two pairs of homologs can segregate in a way
independent of each other, according to Mendel's Second Law? How
this is a random process, we assume that in 50% of the cells the chromosomes
From maternal origin will go to one of the poles and those of paternal origin to the other.

In the other 50%, each of the poles will receive the member of one of the pairs of

paternal origin, while the member of the other pair will be of maternal origin (review it

Figure 6.3 from Lesson 6, to make it clear). Thus, if we could analyze the...
set of gametes obtained from all the germ cells of the individual,
we would expect to observe the formation of 25% of each type. Think about it and discuss
with your colleagues and tutor.

4. Simulate, now, five fertilizations between the male and female gametes of
couple in question. Determine the genotypes and phenotypes of the five resulting children
of these fertilizations:

INDIVIDUAL GENOTYPE PHENOTYPE

1
2

184C E D E R J
5. Build the family pedigree. Discuss with your colleagues the
use of pedigrees in studies of inheritance in the human species.

HEREDOGRAM

6) Calculate the probability that the couple's first child, marrying someone, will be...

normal person in the population, to have a child affected by cystic fibrosis or by

familial hypercholesterolemia.

___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________________
___________________________________________________________________

C E D E R J 185
Basic Genetics
Class 1

1. • What nature presents to us: worm-like beings emerge in corpses.

in decomposition.

The hypothesis is an explanation for why a phenomenon occurs: there is a

spontaneous transformation of decaying matter into worm-like beings.

The deduction is a forecast of what will occur in a certain situation, having

as a basis a provisional explanation for a fact: if there is a transformation
spontaneous matter decomposition into worm-like beings, both in
bottles covered like the open ones should see the emergence of these beings.

The hypothesis test by falsifiability: when conducting the experiment suggested by

from the deduction above, Redi found that the worm-like beings did not appear in the jars

where the decomposing matter was isolated from contact with the flies.
The hypothesis that there is spontaneous transformation should be discarded.
A new hypothesis can be formulated: the worm-like beings are part of the
life cycle of flies.

2. In this exercise, more than one answer may be correct. The important thing is that
you keep in mind what concepts are still not very clear so that
you can understand them later. Don't keep your doubts hidden! This will only
hinder your understanding of other concepts. Note your doubts and check,
throughout the course, if they are being clarified.

a) A hereditary factor, or gene, can be defined in molecular terms as

a segment of a DNA molecule.

b) Hereditary factors are located in the chromosomes, inside the nucleus.

of all the cells in the organism.

c) These factors are transmitted to the next generation through the gametes of
countries that, at the moment of fertilization, come together to form the zygote.

d) Because gene expression is not always straightforward. Recessiveness,

overdominance, sex linkage, variable penetrance and expressivity,
interactions between genes or the simple fact that the allele that conditions the

Character may not have been inherited; possible explanations for this fact.
In this course, you will have the opportunity to learn and deepen your knowledge.

your knowledge about the types of inheritance and gene expression.

188C E D E R J
 e) The duplication of genetic material DNA that precedes cell division.

f) Mutations. Changes in the constitution of hereditary factors can

happen due to flaws during the duplication process or exposure of
genetic material to chemical substances that cause damage to DNA, such as
example, free radicals, teratogens, and some types of radiation.

3. In this exercise, you must reflect not only on the text of the first
classroom, but also about their prior knowledge of the foundations of Genetics.
Remember that doubts only hinder, and that the tutors still do not have
telepathic powers to guess the points where you have the most difficulty.
It all depends on you!

Class 2

1. 1. d
2.a
3.b
4.c
5.e
6.f
7.c
8.a

The centrosome forms the structure responsible for the correct distribution of
chromosomes during cell division. This structure consists of an amorphous material
that involves each pair of centrioles. From them, a set of protein fibers
(microtubules) project towards the opposite poles of the cell, forming the spindle
mitotic. The centrosome has a fundamental role in the orientation of polymerization
these microtubules during spindle formation: the spindle microtubules bind
to the centromeres of the duplicated chromosomes, ensuring the correct distribution of
chromatids in the daughter cells. Before the start of cell division, the centrioles and the others
components of the centrosomes are duplicated, however they remain joined as
a single complex on the same side of the nucleus. At the beginning of mitosis, this complex

divide into two, and each pair of centrioles transforms into a single organizing center
of microtubules.

C E D E R J 189
 3. Ancient scientists did not understand the importance of interphase for the occurrence of
[Link]
for the first time at the beginning of prophase, they already have two chromatids; thus, at some point

momentbetweenitsdisappearanceintelophaseanditsreappearanceinprophase,each
the chromosome must have duplicated. Today, it is known that the duplication of chromosomes

it occurs during interphase. But at that time, this association was not made. As a result,
scientistsreferredtotheinterphasenucleusasrestingnucleus,becauseitwasonlypossible
observe the movement of chromosomes during the stages of cell division.

4. If the gametes were produced by mitosis, it would be expected that each new
thegenerationpresentsdoublethechromosomesduetothejoiningofthetwogametesattheact

from fertilization; since mitosis produces daughter cells with the same number of
chromosomes than the mother [Link], it is essential that there is a mechanism
able to maintain the number of chromosomes of the species in each generation.

5. In this exercise, more than one answer may be correct. The important thing is that
You know how chromosomes should be organized in each one.
the phases of mitosis.

Prophase: 2nd or 3rd schemes of the first row because, in this phase, the chromosomes are already

are found duplicated, condensed and with some degree of organization due to the
linking of the spindle microtubules to the kinetochores of the centromeres; connection
essential for the chromosomes to be able to 'move' during the next stages
of cell division.

Metaphase: 1st scheme of the second line since, at this stage, the chromosomes are already

they are aligned on the equatorial plate of the cell, preparing for division
mitotic.

• Anaphase: 2nd, 3rd, or 4th diagrams of the second line, or even the 1st diagram of the third

line,atthismoment,thesisterchromatidsofeachduplicatedchromosomebegin
to separate, being "pulled" to opposite poles of the cell through shortening
two microtubules of the acromatotic spindle that are attached to the centromeres.

Telophase: 4th or 5th schemes of the third line since at this stage of mitosis,
the migration of the chromatids is completed and the cell membrane begins to divide to
to form two cells containing the same number of pairs of homologous chromosomes
from the initial cell.

190C E D E R J
• Cytokinesis: 2nd, 3rd or 4th schemes of the fourth line, because, at this moment, the division of

The cell membrane completes, forming two identical daughter cells.

6. If your map is different from this template, present it to the tutor for possible
points of doubt can be identified and clarified.

7. Simplified scheme of the phases of mitosis of a cell that has 3 pairs of

homologous chromosomes (2n = 6 chromosomes):

C E D E R J 191
Class 3

Weismann believed that the hereditary substance provided by each of the

parents must be equal or approximately equal to each other. Thus, the cells of
descendants would contain the hereditary information of both parents united. This
it implies that the germ cells of each parent can only contain half
the hereditary information. Weismann then imagined that there must exist a
process that reduced the hereditary material by half during the formation of the
germ cells; a process currently known as meiosis.

In this first stage of meiosis, the pairing of chromosomes occurs.

homologous that allows the exchange of genetic material between them, called
permutation. This stage requires several important events for there to be greater
precision in the pairing of homologous chromosomes, enabling
genetic permutation. This exchange of genetic material is important because it will increase

the genetic variability of the offspring in relation to its parents. An error at this stage
can prevent the permutation from happening.

3. Simplified schemes of the stages of meiosis (I and II) of a cell that has 2
homologous chromosome pairs (2n = 4 chromosomes):

192C E D E R J
4. Simplified scheme of meiosis of another cell from the same organism where the
cromossomos se posicionaram na placa metafásica de forma diferente da apresentada
in the scheme of the previous exercise:

5. A fundamental difference between mitosis and meiosis is that in mitosis there is a

duplication of each chromosome (prophase) for each cell division. This mechanism
maintains the constancy of the number of chromosomes after cell division. In turn,
in meiosis there is only one duplication of chromosomes for two cell divisions:
MeiosisI(reductiondivision)whichreducesthenumberofchromosomesbyhalf;andMeiosisII
(equationaldivision)wheretheseparationofsisterchromatidsofeachchromosomeoccurs.
Another striking difference is the behavior of homologous chromosomes during
metaphase: in mitosis, the homologs align on the equatorial plate, while in
in meiosis the homologs pair up (metaphase I).

6. a) Prophase I 92 chromatids, as all chromosomes are duplicated at this stage.

b) Prophase II 46 chromatids, since the number of chromosomes has been reduced.

at half at the end of the first meiotic division, although they are still found duplicated.

c) Telophase I 46 chromatids, for the same reason as item b.

d) Telophase II 23 chromatids, as the 2nd meiotic division occurs in which the chromatids-
sister chromatids separate, forming haploid cells.

C E D E R J 193
 7. The cells that represent the haploid stages of the life cycle of this fungus
they only have two chromosomes, since their haploid number is n = 2. But in the
diploid stage (transitory diploid meiocyte), two pairs of homologous chromosomes
are present (2n = 4). Note:

!
If you did not get this exercise right, review the concepts of organisms.
haploids and diploids, chromosomes and homologous chromosomes. Remove
your doubts with the tutor. It is very important that you can distinguish
clearly between these concepts.

Class 4

1. a, g, d, h, e, b, f, c.

The peas were advantageous because there were many varieties available,
they were easy to cultivate, their generation time was short, they self-fertilized but
they could also be manipulated to prevent self-fertilization (which allowed the
crossbreeding different varieties through anther cutting and transfer
from the pollen of one plant to the ovary of another) and the descendants obtained by
crosses between different varieties were fertile.

Mendel focused on the analysis of the inheritance of each characteristic individually.

and not of the individual as a whole. In this way, it was able to propose hypotheses that
they explained the pattern of inheritance observed in their experiments. Furthermore, Mendel
did a simple and extraordinary thing when he told the phenotypic proportions of the
prole. Through this counting, Mendel was able to formulate hypotheses to explain
the results found and use mathematical analysis to test and predict
the expected results from your hypotheses.

194C E D E R J
4. Self-fertilization occurs when the male gamete fertilizes the female gamete.
of the same individual, as in the case of a hermaphrodite plant in which the organs
male and female sexual organs are present in the same flower. Cross fertilization
it occurs when the male gamete of an individual fertilizes the female gamete of
another individual, as happens when the pollen produced by a plant's flower
fertilizes the ovule present in the flower of another plant.

5. pea genotype with gray seed coating (dominant): CC

pea genotype with white seed coating (recessive): cc

a) P –CC x cc
F1Phenotypic proportion→ 100% gray-coated peas (Cc)

Genotypic ratio→ 100% Cc

b) P - F1x F1(Cc x Cc)

F1 - Phenotypic ratio→ 3 peas with gray coating (C): 1 pea -

with white coating (cc)

Genotypic ratio→ 1 cc : 2 cc : 1 cc

c) P – F1white-coated pea (Cc x cc)

F1Phenotypic ratio→ 1 pea with gray coating (Cc): 1 pea
with white coating (cc)

Genotypic proportion→ 1 cc : 1 cc

6. We could do a test cross, that is, a cross of the plant in

issue with a homozygous recessive plant (aa) for the same characteristic. This
what type of crossing is done when one wants to determine the genotype of an individual
with a dominant phenotype. Thus, the identification of the individual's genotype
testing is done through the visualization of the phenotype of the offspring, since the tester individual

is homozygous recessive, contributing only recessive alleles to the offspring.

For example:

If the tested individual is AA, that is, pure according to Mendel's criteria:

AAxaa(testerindividual)→ 100%oftheoffspringwiththedominanttrait(Aa).

If the tested individual is Aa, that is, hybrid according to the criteria of Mendel:

Aaxaa (testing individual)→ 50% of the offspring with dominant trait (Aa)
50% of the offspring with recessive characteristics (aa).

CEDERJ 195
 7. Observed at the intersection:

P - plant with crenate leaves x plant with lobed leaves

F1phenotypic ratio→ 100% lobed leaves

I cannot agree with the producer, since the factor that conditions the
the created form may have been passed on to the offspring but not expressed, due to
to be recessive, for example.
Hypothesis to explain the obtained result: the crenate leaf characteristic is
recessive (l) with respect to the lobed leaf characteristic (L), and therefore plants with
notched leaves (ll) did not appear in F1 (100% Ll).
•Testing the proposed hypothesis: crossing the F1 with each other. If plants appear
with crinkled leaves in F2, the results observed in this cross will be
according to the expected results from the proposed hypothesis. Thus, we will be able to
reject the hypothesis proposed by the producer, in which the factors that condition
the crenated form would not have been passed on to the F1 generation.

8. Observed at the intersections:

P - gray mice x white mice (albino)

F1phenotypic ratio→ 100% gray
F2phenotypic ratio→ 198 greys : 72 albinos≈ 3 grays: 1 albino
a total of 270 mice

Hypothesis: the gray characteristic is dominant (C) over the albino characteristic (c).
Expected by the proposed hypothesis:

P –CCxcc
F1phenotypic ratio→ 100% gray
genotypic ratio→ 100%Cc
F2phenotypic ratio→ 202,5 cinzas : 67,5 albinos (3 cinzas : 1 albino)
genotypic proportion→ 1CC: 2Cc: 1cc
The expected results from this hypothesis are consistent with the results.
observed in the experiment.

9. genotype of the normal woman (carrier of the factor for albinism): Aa

genotype of the albino man: aa
a. P – Aa x aa
F1Expected genotypic and phenotypic ratios in the F generation1due to the fertilization of
male gametes ( ) and female gametes ( ) of the parental generation (note that only one

the type of male gamete that can be produced by an individual with genotype aa):

genotypic ratio→ 1 Aa : 1 aa
A a
phenotypic ratio→ 1 normal (Aa) : 1 albino (aa)
a Aa aa

196C E D E R J
 b. P – Aa x Aa
F1Expected genotypic and phenotypic proportions in the F generation1;
due to the fertilization of male (♂) and female (♀) gametes of the parental generation:

♀ A a genotypic ratio→ 1 AA : 2 Aa : 1 aa
♂
phenotypic ratio→ 3 normals (A_) : 1 albino (aa)
A AA Aa

a Aa aa

10. Observed at the intersections:

Intersection I:

P - bull without horns x cow I with horns

F1calf without horns

Crossing II:

P - bull without horns x cow II with horns

F1bull calf with horns

Intersection III:

P - bull without horns x cow III without horns

F1calf with horns

a) Hypothesis: the hornless bull is heterozygous (Cc), cows I and II with horns are
recessive homozygous (cc) and cow III without horns is heterozygous (Cc).

b) Expected by the proposed hypothesis:

Intersection I:

P - bull without horns (Cc) x cow I with horns (cc)

F1hornless calf (Cc)

Crossing II:

P - bull without horns (Cc) x cow II with horns (cc)

F1calf with horns (cc)

Crossing III:

P - bull without horns (Cc) x cow III without horns (Cc)

F1- calf with horns (cc)

The expected results of this hypothesis are in accordance with the results.
observed in the experiment.

C E D E R J 197
 Class 5

1. d

2. c

3. When two or more characteristics with contrasting states are involved,

we can verify that the ratio 3 : 1 is still maintained if we consider each
characteristic individually, due to the independent segregation of factors.

Example: the expected phenotypic ratio of a self-fertilization of double peas

heterozygous smooth-yellow (RrVv) is 9 smooth-yellow (R_V_) : 3 smooth-green (R_vv) :
3 rough-yellow (rrV_): 1 rough-green (rrvv).

If we consider the characteristics individually:

1 –crossing between smooth (Rr x Rr) → 3 smooth (R_) : 1 rough (rr)→ logo, o
phenotypic probability of 3/4 of appearing in the offspring, while
the wrinkled phenotype has a 1/4 probability.

2 - crossing between yellows (Vv x Vv)→ 3 yellows (V_) : 1 green (vv)→

The yellow phenotype has a probability of 3/4 of appearing in the offspring.
while the phenotype has 1/4 probability.

Considering the probabilities that each phenotype has of appearing in the offspring,
we can expect that in a hybrid crossing:
The probability of appearing smooth-yellow (R_V_) = 3/4 x 3/4 = 9/16
The probability of appearing smooth-green (R_vv) = 3/4 x 1/4 = 3/16

The probability of appearing rough-yellow (rrV_) = 1/4 x 3/4 = 3/16

The probability of appearing rough-green (rrvv) = 1/4 x 1/4 = 1/16
Therefore, the ratio 9 : 3 : 3 : 1 can be derived from the ratio 3 : 1

4. a. The following conditions could be considered facts for the model

Mendelian law would be valid: in each pair of contrasting hereditary factors (this
One member of the pair should be dominant while the other member
should be recessive; and the dominant and recessive hereditary factors do not
would be modified when they occurred together in the hybrid, that is, the offspring of

a cross between hybrids would display both the dominant characteristic

as for the recessive, without any modification in the phenotype.

b. The basic difference between the 1st and 2nd Laws of Mendel is that while the 1st deals with
from the segregation of a pair of factors, the second refers to segregation into more than
a couple of factors.

198C E D E R J
5. genotype of tall pea and swollen pod (dominant states): AAEE

genotype of dwarf pea and depressed pod (recessive states): aaee

a. P – AAEE(1) xaaee(2)

F1Expected genotypic and phenotypic ratios in the F generation1due to the fertilization of

gametes of the plants from the parental generation (1 or 2):

1 AE
2
ae AaEe

genotypic proportion→ 100%AaEe

phenotypic ratio→ 100% high pea and swollen pod

b. P –AaEe(1) xAaEe(2)
F1–
1
AE Ae aE ae
2
AE AAEE AAEe AaEE AaEe

Ae AAEe AAee AaEe Aaee

aE AaEE AaEa aaEE aaEe

ae AaEe Aaee aaEe aaee

genotypic ratio→ ["1AAEE","2AAEe","1AAee","2AaEE","4AaEe","2Aaee"]

1aaEE: 2aaEe: 1aaee

phenotypic ratio→ high pea and swollen pod (A_E_): high pea
e vagem deprimida (A_ee) :3ervilha anã e vagem inflada (aaE_) :1ervilha anã
and depressed (aaee)

c. P –AaEe(1) xaaee(2)

F1– 1
2 AE Ae aE ae
ae AaEe Aaee aaEe aaee

genotypic proportion→ 1AaEe: 1Aaee: 1aaEe: 1aaee

phenotypic ratio→ Tall pea and inflated pod (AaEe) : Tall pea
depressed pod (Aaee): dwarf pea and inflated pod (aaEe): dwarf pea
is depressed (aaee)

C E D E R J 199
 6. I) 4 types (ABCd, AbCd, aBCd, abCd)

B – C – d (1st type)

b - C - d (2nd type)

B - C - d (3rd type)

b – C – d (4th type)

II) 8 types (ABC, ABc, AbC, Abc, aBC, aBc, abC and abc)

C (1st type)

c (2nd type)

C (3rd type)

c (4th type)

C (5th type)

c (6th type)

C (7th type)

c (8th type)

200C E D E R J
 III. 8 types (AbCDE, AbCDe, AbcDE, AbcDe, abCDE, abCDe, abcDE, abcDe)

E (1st type)

C – D

e (2nd type)

A - b

E (3rd type)

c – D

e (4th type)

E (5th type)

C – D

e (6th type)

a - b

E (7th type)

c – D

e (8th type)

7. c

8. e

9. b

10. a

11. d

C E D E R J 201
 12. a) 8 types of gametes.

b) 27 types of combinations.

c) Phenotypic reasons determined by each pair of factors.

Phenotypes
Seeds Seeds seed coatings Phenotypic ratio
lisa x rugosa yellow x green gray x white expected in F2

3/4
= 27/64 yellow lisas
with gray wrapping.
Gray

3/4

Yellow
1/4
= 9/64 yellow lilies with
3/4 white coverage.
White
= 9/64 green laces with
Lisa
gray coverage.
3/4Gray

1/4

Green

1/4
= 3/64 green lilies with
white coverage.
White

9/64 yellow rough

with gray cover.
3/4 Gray

3/4

Yellow
1/4 = 3/64 yellow rugosas
with white cover.

White
3/64 green rugosas
1/4 Rugosa with gray cover.
3/4Gray

1/4

Green

1/64 green rugosas

with white cover.
1/4 White
202C E D E R J
 Class 6

1. g

2. a

3. b

4. d

5. f

6. e

7. c

8. h

9. a

10. b

11. dominant linked to the X chromosome.

12. genotype of the female with long and straight tail: XbXb

genotype of the male with short and twisted tail: XBY

P - XbXbx XBY

F1 - ♂ XB Y
♀
Xb XBXbXbY

expected phenotypic ratio→ 100% of the females with short tails and

twisted (XBXb100% of males with a long and straight tail (XbY)

13. genotype of the short-winged female: XmXm

genotype of the long-winged female: X+X+ or X+Xm

genotype of the short-winged male: XmY

genotype of the long-winged male: X+Y

a. P – XmXmx XmY

F1– ♀ ♂ Xm Y
Xm XmXmXmY

phenotypic ratio→ 100% short bases (XmXme XmY).

C E D E R J 203
 b. P – XmXmx X+Y

F1– ♂
♀ X+ Y
Xm X+XmXmY

phenotypic ratio→ 100% of the long-winged females (X+Xm).

100% of short-winged males (XmY).

c. P – X+X+ x XmY

F1– ♂ Xm Y
♀
X+ X+XmX+Y

phenotypic ratio→ 100% long straps (1 X+Xm1 X+Y).

d. P – X+Xmx X+Y

F1– ♀ ♂ X+ Y
X+ X+X+ X+Y

Xm X+XmXmY

phenotypic ratio→ 100% long-winged females (X) +X+ e X+Xm), 50% of

long-winged machos+Y) and 50% of short-winged males (XmY).

e. P – X+Xmx XmY

F1–
♂ Xm Y
♀
X+ X+XmX+Y

Xm XmXmXmY

phenotypic ratio→ 50% of female long-winged (X+Xm) 50% of the females

of short wings (XmXm50% of long-winged males (X+Y) and 50% of the males
of short wings (XmY).

204C E D E R J
14. genotype of the barred feather female and homozygous for pink comb: ZBWRR
genotype of the male with non-striped feathers and a simple comb: ZbZbrr

P – ZBWRRx ZbZbrr

F1– ♀ ZB R WR
♂
Zb r ZBZbRrZbWRr

expected phenotypic ratio→ 100% of the males with barred feathers and
pink crestBZbRr) and 100% of the females with non-barred feathers and pink crest
(ZbWRr)

Note: Remember that in birds, sex determination is done by the ZZ system.

ZW, in which female is the heterogametic sex (ZW) while male is the
homogametic sex (ZZ).
Class 7

Activity 1: present your model for discussion with your colleagues and tutors.

Activity 2:

1. Human chromosomes are classified into seven groups (from A to G) according to

with size and morphology. Additionally, the autosomes are numbered from
1 to 22 by size.

Group A: comprises the three largest chromosomal pairs.

Chromosomes from pairs 1 and 3 are metacentric, and those from pair 2 are
submetacentric.

Group B: pairs 4 and 5, submetacentric. The size of their short arms

is equivalent to 1/3 of your long arms.

Group C: a total of 14 chromosomes. Since pairs cannot be identified

of chromosomes by morphological analysis, these chromosomes must be
organized in descending order of size.

Group D: consists of pairs 13, 14, and 15. They are acrocentric, of medium size.
with the presence of satellites in the short arms. These satellites are small
terminal spheres not always visible.

CEDERJ 205
 Group E: pair 16, metacentric, and pairs 17 and 18, submetacentric, being that
The short arms of pair 17 are slightly larger than those of pair 18.

Group F: the chromosomes of pairs 19 and 20 constitute this group and are the
human metacentric chromosomes minors.

Group G: consists of chromosome pairs 21 and 22. These are the smallest.
human acrocentric chromosomes and may present satellites, not always
visible, on the short arms.

For sexual: in women it is formed by a pair of X chromosomes, while

in men consists of a pair of non-homologous chromosomes, the
X and Y chromosomes. The Y chromosome is acrocentric and can be differentiated.
two pairs 21 and 22 due to the parallel position of the larger arms and the absence of

satellites.

Note: The chromosomes of groups B, C, D, F, and G cannot be identified.

only by analyzing its morphology.

2. Activity to be developed by the student and discussed with their peers

tutors.

3. Activity to be developed by the student and discussed with their classmates and
tutors.

206C E D E R J
Activity 3:

There is more than one way to complete this scheme. Check if your answer is correct.
is correct with your colleagues and tutors.

C E D E R J 207
 2.

• At the end of meiosis of this cell, only two types of gametes were formed.
with the genotypes cdY or CDXe.

• The other types of gametes can be formed from different

alignments of paired chromosomes during metaphase I of others
meiotic cells.

3. When we consider all the meiotic cells of this individual (CcDdXeY),

we can conclude that this individual will form 8 types of gametes in the proportion of

1:1:1:1:1:1:1:1. Observe the following branch method for determining the types
of gametes formed.

If it were a female CcDdXEXe8 types of gametes would be formed in

proportion of 1:1:1:1:1:1:1:1. Note:

208C E D E R J
 Class 8

activity to be developed by the student and discussed with colleagues and tutors.

2. 2.1) c
2.2) d
2.3) c, a
2.4) a, b
2.5) f
2.6) and
2.7) g
2.8) f
2.9) e
2.10) j
2.11) i
3. a) The petal of a homozygous plant for a recessive mutation that
the first reaction should be white, since this plant does not
will produce the enzyme necessary to transform the initial color substance
white in the intermediate substance of blue color. Note that even if this plant
possess the normal enzyme D capable of transforming the intermediate substance
of blue color in the final purple color pigment, this plant has no capacity
to produce the intermediate substance and, therefore, cannot produce the
final pigment.

b) The petal of a homozygous plant for a recessive mutation that prevents

the second reaction should be blue. This plant is capable of transforming the substance
initial in the intermediate substance, as it possesses the normal enzyme B, but does not

is capable of producing the necessary enzyme D to transform the substance

blue intermediate in the final purple pigment.

c) The cited plant has the genotype bbD_, while the cited plant has
has the genotype B_dd.

4. Probably, 10 units of the enzyme are not sufficient to produce the

normal phenotype. Thus, heterozygous and homozygous individuals for the
mutant alleles produce the same phenotype, a case of haplo-insufficiency. In this
In this case, the mutant allele is the dominant allele.

5. This disease should be inherited with a recessive phenotype, since only

a normal allele (dominant) is sufficient to produce the normal phenotype, that is,
is haplo-sufficient. Thus, a heterozygous individual will show a normal phenotype
for possessing one of the dominant alleles.

C E D E R J 209
Class 9

1.

A B C D E F

Autosomal recessive S N S S S S

Autosomal dominant N S S S N S

X-linked recessive S N S N N S

Linked to the dominant X N N N S N N

Linked to Y N N N N N N

2. a) Autosomal dominant.

b) Linked to the dominant X.

c) X-linked recessive.

d) Autosomal recessive.

3. a)

b) Autosomal recessive.

c) 25%, since both parents are heterozygous.

d) Catarina (II-2), her husband (II-1), Elisa (I-3) and Bárbara (I-2)

4. a) Autosomal dominant.

b) I-1, I-4, II-3, II-4, II-6, II-7, III-2 and III-5.

c) I-2, I-3, II-1, II-2, II-5, II-8, III-1, III-3 and III-4.

d) From the analysis of this pedigree, we can conclude that both

individuals III-3 and III-4 are certain heterozygotes (Aa). Therefore, the probability
this couple having three children, one without character and two with character,
regardless of sex and birth order, it can be deduced through
of Newton's binomial:

210C E D E R J
 P = [3! / (1!2!)] (1/4)1(3/4)2

P = [3x2x1 / (1x2x1)] x 1/4 x 9/16

P = [6/2] x 9/64

P= 27/64≈ 42.2%

5. Considering each character separately, we can observe that the condition

Dental enamel deficiency shows a dominant X-linked inheritance.
since the affected mother (X X) A
hada an affected child (X Y) and another
A normal one (X Y). a

Your turn, the inheritance of color blindness is linked to the recessive X, since the woman (X X) is the daughter. D d

d and a normal mother (X X_) does not

from an affected father (X Y) D express this condition.

If color blindness were linked to the dominant X, this woman should be affected by it.
to be a daughter of an affected father.

D express
How can the children of a normal mother (X X) d this condition, while
that she is not affected herself, the inheritance of color blindness cannot be linked to the X

dominant.

AD ad
Thus, we can say that the mother's genotype is X X, and the genotype of the children is

XAdY for the son with dental enamel deficiency and color ad
blindness and X Y for the son
with normal dental enamel and color blindness. Note that the son with genotype X Y is Ad

fruit of a gamete that underwent recombination between these genes.

6. From the analysis of this pedigree, we can deduce the probability that the
individual IV-1 to be affected through the following steps:

Probability of III-2 being heterozygous = 2/3

As your brother III-3 is a double homozygous recessive (affected - aa) we can

to deduce that your mother II-2 and your father (who does not appear in the pedigree) are

heterozygous. Considering the four genotypic possibilities resulting

from a crossing between heterozygotes (AA, Aa, Aa, aa) the probability of III-2
the heterozygous being will have 2 chances am3, because definitely this individual

it cannot be aa (AA, Aa, Aa, aa).

2. Probability of III-1 being heterozygous: 1/2 x 1/2 (probability of his mother)

II-1 received the recessive allele from one of the parents x probability of itself
individual III-1 having received the recessive allele from his mother) = 1/4

C E D E R J 211
 Probability of III-2 and III-1 being heterozygous: 2/3 x 1/4 (probability
the probability of III-2 being heterozygous x the probability of III-1 being heterozygous) = 1/6

4. Probability of III-2 and III-1, being heterozygous, having an affected child

(individual IV-1): 1/6 x 1/4 (probability that III-2 and III-1 are heterozygous)
probability of individual IV-1 being double homozygous recessive - affected
1/24

Therefore, the probability of individual IV-1 being affected is 1/24≈ 4.2%

Note: When analyzing a pedigree of a recessive anomaly, we must

consider that the individuals coming from the population, that is, the individuals
non-affected members of the population who marry someone from the family, are

dominant homozygotes (AA, for example). This is because it is very small.

the chance of an individual from the general population being a carrier (Aa) of the allele

recessive of that specific gene that causes the disease in the analyzed family.
Meanwhile, the chance of an unaffected individual from the family in question carrying
a recessive allele, that is, being heterozygous (Aa), will depend on the analysis of the

phenotype and genotype of their ancestors and, when possible, the analysis of
your descendants.

212C E D E R J