BIOL 3233 Genetics

Chromosome Heredity
Chapter 3
 Reading
Cover the following section in your text:
Section 3.3 -3.5
 3.3 The Chromosome Theory of Heredity Proposes
That Genes Are Carried on Chromosomes

Morgan studied fruit flies, Drosophila

melanogaster, to test Mendel’s rules on a
natural (wild fly), rather than domesticated,
species (pea plant)

To start he need flies (lots of flies!)

Mostly found “wild type” which signifies the

phenotype most common in a population

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 Fruit Flies as model organisms

1. Easily contained
2. Easily feed (corn-meal, sugar and water)
3. Life cycle is 12 and 14 days depend on
conditions
4. 25 to 30 generations could be raised in a
year (compared to 8-9 generations per year
for mice)
5. For genetics it is all about large number of
offspring over the short time possible
6. Very difficult to work with humans
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 X and Y Chromosomes
• Nettie Stevens studied chromosome
differences between male and female beetles
(Tenebrio molitor)

• She found that diploid cells of females

contained 20 large chromosomes but those
of males contained 19 large chromosomes
and one small one

• Half of the sperm of males contained 10 large

chromosomes and the other half had 9 large
and one small chromosome

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 X-Linked Inheritance
• Stevens concluded that sex-dependent
hereditary differences are due to the
presence of two X chromosomes in females
and an X and a smaller Y chromosome in
males

• Sex-linked inheritance refers to

transmission of traits on sex chromosomes

• In 1910, Morgan’s experiments with flies

validated Steven’s conclusions
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 The White-Eye Mutant
• The first mutant identified in Morgan’s lab
was a male with white eyes instead of the
normal red color (This alone took an entire
year!)

• Now we are in business! The mutant white-

eyed male was crossed to a normal red-eyed
female, producing many F1, all with red eyes

• Thus the white-eyed mutant allele was

recessive
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Wild – type Red eye Mutant White eye

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 F1 Intercrossed
• When the F1 progeny were interbred, the F2
offspring consisted of 1101 red-eyed males,
782 white-eyed males, and 2459 red-eyed
females

• This is not a normal 3:1 ratio, because there

are phenotypic differences between male and
female progeny

• Only males had white eyes! (x-linked

inheritance)
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 Additional Crosses
• When the original white-eyed male was
crossed to one of the F1 females, a 1:1 ratio
of white eyes and red eyes was observed in
both male and female offspring

• A cross between a white-eyed female and

red-eyed male produced red-eyed female
and white-eyed male F1; a cross between
these produced F1 with red and white eyes in
equal frequencies among both male and
female progeny

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 The Gene for Eye Color Is on the X
Chromosome

The differences in phenotype according to gender

are not anticipated according to Mendel’s laws

The transmission of the X chromosome can account

for the results obtained by Morgan’s lab

X-linked inheritance is the term for traits carried on

the X chromosome; males have only one X and so
are called hemizygous for X-linked traits

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 Sex Linked Disorders
Some disorders caused by recessive alleles
on the X chromosome in humans:
– Color blindness
– Duchenne muscular dystrophy (Absence of a
key muscle protein dystrophin and mapped the
gene to the X chromosome)
– Hemophilia (Absence of one or more of the
blood proteins required for clotting)
If a color-blind woman married a
man who had normal color vision,
what would be the probable
phenotypes of their children?
 XNXN  XnY XNXn  XNY XNXn  XnY

Sperm Xn Y Sperm XN Y Sperm Xn Y

Eggs XN XNXn XNY Eggs XN XNXN XNY Eggs XN XNXn XNY

XN XNXn XNY Xn XnXN XnY Xn XnXn XnY

(a) (b) (c)

 XNXN  XnY XNXn  XNY XNXn  XnY

Sperm Xn Y Sperm XN Y Sperm Xn Y

Eggs XN XNXn XNY Eggs XN XNXN XNY Eggs XN XNXn XNY

XN XNXn XNY Xn XnXN XnY Xn XnXn XnY

(a) (b) (c)

 XNXn  XNY

Sperm XN Y

Eggs XN XNXN XNY

Xn XnXN XnY

(b)
 XNXn  XNY

Sperm XN Y

Eggs XN XNXN XNY

Xn XnXN XnY

(b)
 XNXn  XnY

Sperm Xn Y

Eggs XN XNXn XNY

Xn XnXn XnY
 XNXn  XnY

Sperm Xn Y

Eggs XN XNXn XNY

Xn XnXn XnY
 Analysis of Nondisjunction
Morgan’s work led him to propose the chromosome
theory of heredity

Calvin Bridges studied unexpected eye color

phenotypes and abnormal chromosome numbers

For example, in a cross between a white-eyed

female and red-eyed male, unexpected rare
(1/2000) offspring were observed: females with
white eyes or males with red eyes
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 Explanation of Unusual Phenotypes
Bridges saw that the exceptional females had three
X chromosomes and one Y; and the exceptional
males had just one X chromosome

The exceptional phenotypes resulted from rare

mistakes in meiosis caused by the failure of X
chromosomes to separate correctly in either
meiosis I and II

Failed chromosome separation is nondisjunction

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 Chromosome theory of heredity

Bridges observations lead to conclusive proof

of the chromosome theory of heredity

He showed that the white (w) allele segregates

with the X chromosome during normal meiosis
and during nondisjunction.

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 3.4 Sex Determination Is Chromosome and
Genetic
Sex determination involves the genetic and
biological processes that produce the male and
female characteristics of a species

Chromosomal sex is the presence of

chromosomes characteristic of each sex and is
determined at the moment of fertilization

Phenotypic sex is the internal and external

morphology of each sex, and results from
differences in gene expression
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 Sex Determination in Drosophila
Bridge’s study of nondisjunction confirmed
chromosome theory and provided information about
sex determination

Key Features: Females have two X chromosomes

and males have one X chromosome

Thus in flies:
Males = X0, XYY, or XY (normal)
Females = XXY or XX (normal)
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 The X/Autosome Ratio
• The X/A ratio or X/autosome ratio
determines gender based on the number of
X chromosomes to sets of autosomes

• Males have an X/A ratio of 0.5 and females

have a ratio of 1.0

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 Mammalian Sex Determination
Placental mammals have X and Y chromosomes

However in mammals it is most dependent on the Y

chromosome

Sex determination depends on the presence or absence of a

single gene, SRY, found on the Y chromosome

In mammals, males can be XY (normal), XXY, or XYY; females

are XX (normal), XO, or XXX

SRY is a transcription factor needed for male-specific gene

expression
Lack SRY expression and development will occur as female
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 SRY
• Early mammalian embryos have clusters of
tissue called undifferentiated gonads, which
can develop as ovaries or testes

• Expression of SRY initiates testicular

development of the undifferentiated gonads

• The absence of SRY expression allows the

default, female state, to develop

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 Diversity of Sex Determination
A different system, the Z/W system, is used by birds,
some reptiles, some fish, butterflies, and moths

In this system females have two different sex

chromosomes (ZW) and males have two sex
chromosomes that are the same (ZZ)

Sex chromosomes of the platypus consist of 5 pairs of

sex chromosomes with 5 XY pairs in males and 5 XX
pairs in females

These multiple sets of sex chromsomes have been seen

in some plants, termites and spiders
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 3.5 Human Sex-Linked Transmission Follows
Distinct Patterns
In X-linked recessive inheritance, females
homozygoous for the recessive allele or males
hemizygous for it display the recessive phenotype

In X-linked dominant traits, heterozygous females and

males hemizygous for the dominant allele express the
dominant phenotype

Recessive and dominant in this case ONLY refers to

females
Reason:
Hemizygous males display any allele on their single X
whether the allele is recessive or dominant in females
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 Expression of X-Linked Recessive Traits

A hallmark of recessive X-linked inheritance is

the expression of the trait much more often in
males than in females

All males express the trait but only

homozygous females express the trait

There are numerous X-linked recessive traits

in humans (Table 3.2)

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 Features of X-Linked Recessive
Inheritance
1. Many more males than females have the trait due to
hemizygosity

2. A recessive male mated to a homozygous dominant

female produces all offspring with the dominant
phenotype, and all female offspring are carriers

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 Features of X-Linked Recessive
Inheritance
3. Matings of recessive males with carrier females
give half dominant and half recessive offspring of
both sexes

4. Matings of homozygous recessive females with

dominant males produce all dominant (carrier)
female offspring and all recessive male offspring

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 Hemophilia A Is an X-Linked Recessive
Trait
Hemophilia A is caused by a mutation in the
factor VIII gene on the X chromosome

The mutant allele produces a nonfunctional

blood-clotting protein

A de novo (newly occurring) mutation is

thought to have been passed from Queen
Victoria of England to some of her offspring

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 X-Linked Dominant Trait Transmission

The distinctive characteristics of X-linked

dominant traits are
1. Heterozygous females mated to wild-type males
transmit the dominant allele to half their progeny of
each sex
2. Dominant males mated to homozygous recessive
females pass the trait to all their daughters and
none of their sons
3. The trait appears equally frequently in males and
females

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 Congenital Hypertrichosis
Congenital hypertrichosis
(CGH) is a rare X-linked
dominant disorder in
humans

It leads to a large
increase in the number of
hair follicles on the body,
and males and females
have more body hair than
normal

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X-Linked Dominant Trait Transmission
Pedigree of a family with CGH

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 Y-Linked Inheritance
Y-linked traits are transmitted in an exclusively
male-to-male pattern

In mammals, there are fewer than 50 genes on

the Y chromosome; many play roles in male sex
determination or development

Though males have only one Y chromosome,

they are not hemizygous for it, as most of the
genes on the Y are present in two copies
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 The Pseudoautosomal Region
Two small regions of homology, the
pseudoautosomal regions (PAR1 and PAR2),
exist between the X and Y chromosomes

These allow homologous pairing between the X

and Y at meiosis

There is evidence that crossing over occurs

within these regions during meiosis

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 3.6 Dosage Compensation Equalizes Dosage of
Sex-Linked Genes
In organisms with sex chromosomes, there is a
gender imbalance between the copy number of
genes on the sex chromosomes

Any mechanism that compensates for the

difference in number of copies of genes between
males and females is called dosage
compensation

There are at least three different mechanisms of

dosage compensation
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 Random X-Chromosome Inactivation in
Placental Mammals
Early in mammalian development, one of two X
chromosomes in each female somatic cell is
randomly inactivated

The random X inactivation hypothesis is also

called the Lyon hypothesis, after Mary Lyon,
who first proposed it (1962)

The inactive X chromosome is visible near the

nuclear wall, as a condensed Barr body, first
visualized by Murray Barr (1949)
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 Female Mammals Are Mosaics
Once X inactivation has occurred in a cell, it is
permanent in all the descendants of that cell

Female mammals are mosaics of two

populations of cells; one expresses the
maternal X and the other the paternal X

Alleles of both chromosomes are expressed

approximately equally over the whole organism

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 Calico and Tortoiseshell Cats Are Visibly
Mosaic
• In cats, the X chromosome
carries a gene responsible
for coat color

• One allele specifies a black

color; the other a yellow
color

• X inactivation in
heterozygous females leads
to a pattern of orange and
black patches that is unique
to each individual

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 Mechanism of X Inactivation
Random X inactivation requires an X-linked gene
called Xist (X-inactivation-specific-transcript)

The gene produces large RNA molecules that

spread out and cover (or paint) the chromosome to
be inactivated

Xist can only act on the chromosome from which it

is being transcribed and not the homolog (i.e., it
acts
in cis)
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