BIO REVIEWER

Bio Reviewer

The Cell Cycle

What is cancer?
-​ It is a large group of diseases that can start in almost any organ or tissue and transfer to
other parts of the body.
Why do people develop cancer?
-​ Genetic, Environmental, Lifestyle factors
How does cancer happen?
-​ Abnormal cells grow and reproduce uncontrollably, go beyond their usual boundaries to
invade adjoining parts of the body and/or spread to other organs.

DNA in the Cell Cycle

DNA in Eukaryotes
DNA in Eukaryotes

Where are the genes?

Homologous Chromosomes
-​ 22 pairs are autosomes while the other pair is the sex chromosomes (XX or XY)
-​ In sex cells, homologous chromosomes pair and then separate during meiosis

Ploidy Levels
Haploid
-​ cell contains only one set of chromosomes
-​ Sex (Gametic) cells and spores only
-​ Denoted as n
-​ n = 23 chromosomes in humans

Diploid
-​ cell contains two sets of chromosomes
-​ All other cells in the body
-​ Denoted as 2n
-​ 2n = 46 chromosomes in humans

What is the cell cycle?

 -​ the stages undergone by every cell in an organism as time goes by

Cell Cycle
Interphase
Non-dividing phase where:
-​ cell grows
-​ nutrients accumulate
-​ DNA replicates
-​ nuclear envelope still visible
-​ DNA in chromatin form

Stages of Interphase
1.​ Gap/Growth 1 (G1) - young cells
-​ undergoes rapid growth and attains normal size
-​ forms organelles
-​ longest phase
-​ Muscle and nerve cells remain at this stage throughout their life cycle
2.​ Synthesis (S) - DNA in chromatin form
-​ DNA doubles by DNA replication
-​ By the end, we will have enough DNA volume to form 2 sister chromatids
-​ Number of chromosomes doubles
-​ Centrosome also duplicated where each will give rise to spindle fibers

RECALL:
-​ Centrosome found in cytoplasm
-​ Centrosome is made of 2 centrioles
-​ Centrioles are perpendicular
RECALL:
-​ Nondividing cells have separate centrioles, one near nucleus. Both help in organizing
microtubule network.
-​ May form a Basal body, where centrioles attach to the inner side of cell membrane
-​ In cells with flagellum and cilia, the basal body serves as the site of attachment to
microtubule

-​ Egg cells lose their centrioles which are restored by sperm

Before mitosis, these move apart until they’re on opposite sides of the nucleus.
During cell division, they grow spindle fibers

SPINDLE FIBERS:
-​ Attach to kinetochore
-​ Some bind to chromosome arms
 -​ Others continue until they extend between each other in an overlap

3.​ Gap/Growth 2 (G2)

-​ Restores energy and creates proteins necessary for next step
-​ Cell organelles duplicated
-​ Cytoskeleton dismantled and recycled
-​ Additional growth

The M-Phase
Multiplying by Dividing

Cell Division
Unicellular organisms:
●​ Cell division = Reproduction (Asexual)
●​ Binary fission, Budding

Two stages:
●​ Karyokinesis - division of nucleus
●​ Cytokinesis - division of cytoplasm

Functions of Cell Division

What is Mitosis?
-​ Cell division undergone by somatic or body cells for growth, development, repair,an
asexual reproduction
-​ Daughter cells have the same number of chromosomes as the parent cell
Stages of Mitosis

Prophase
-​ chromatin microscopically visible and condenses into randomly-arranged chromosomes
composed of sister chromatids
-​ Centrosomes migrate to cell’s opposite ends
-​ Spindle fibers form and attach to chromosome
-​ Nuclear membrane dissolves
-​ Nucleolus becomes invisible

Metaphase
-​ All chromosomes move and form a single line at the center called metaphase plate
-​ This alignment ensures that each daughter cell will receive the same number and type of
chromosomes
 -​ Forms random orientation of chromosomes

Anaphase
-​ The spindle fibers attached to the centromeres shorten, pulling the sister chromatids
apart
-​ Each pole (centriole) receives one chromatid

Telophase
-​ Chromatids now on opposite poles
-​ Nuclear membrane forms around each pole
-​ Chromatids become chromatin again
-​ Spindle fibers disassemble

Cytokinesis
-​ Starts in either anaphase or telophase but completes AFTER telophase. Here, the
cytoplasm of the cell is divided into two daughter cells.

Post-Mitosis
-​ Both cells enter interphase, and the cycle may begin again
-​ Each daughter cell is genetically identical and has same ploidy level
Cell Cycle Checkpoints
-​ A group of proteins at the end of each phase used to check if the cell can proceed
1.​ G1 Checkpoint
-​ checks if cell is ready for DNA synthesis or S phase
2.​ G2 Checkpoint
-​ checks if cell is mature enough to divide or undergo M phase
3.​ M Checkpoint
-​ occurs during metaphase
-​ checks if the cell is ready to finish cell division

Green - everything is good, PROCEED

Yellow - Something is wrong, LETS FIX IT
Red - Something’s wrong and we can’t fix it, APOPTOSIS!

(colors aren’t accurate but they’re just for understanding)

Meiosis
-​ used by multicellular organisms to form reproductive cells like sperm and egg of plants
and animals, and spores of fungi and ferns
-​ daughter cells have half the number of chromosomes as the parent (haploid)
-​ produces four genetically unique daughter cells

Meiosis I: Reductional
 -​ Reduces the number of chromosomes into haploid level

Meiosis II: Equational

-​ Very similar to mitosis

Prophase I
-​ The chromosomes condense and the nucleolus breaks down
-​ Homologous chromosomes pair by the process called synapsis
-​ As chromosomes move around, crossing over happens - this means genetic material
can be exchanged

Metaphase I
-​ Homologous chromosomes align in pairs in the center of the cwll
 -​ Random assortment occurs - chromosome pairs line up randomly

Anaphase I
-​ Chromosome pairs separate and move to opposite ends of the cell
-​ This ensures each cell contains half the number of chromosomes (haploid)

Telophase I
-​ Two new nuclei form around each set of chromosomes
-​ The cytoplasm splits and two (haploid) daughter cells are formwd
Prophase 2
-​ Phase 2 happens to allow 4 haploid sex cells (sperm and egg cells) to be created
-​ The chromosomes condense and the nucleolus breaks in both cells

Metaphase 2
-​ The chromosomes align single file in the center of the cell
-​ This occurs to ensure sister chromatids separate in the next stage
Anaphase 2
-​ Sister chromatids separate and move to opposite ends of the cell
-​ This ensures the daughter cells remain haploid - that means that they have half the
genetic material of the original parent cell

Telophase 2
-​ Four new nuclei form around each set of chromosomes
-​ The cytoplasm split and four (haploid) daughter cells are formed

Mitosis in Action
DNA DURING MEIOSIS

Maintaining Ploidy Levels: Meiosis

Checkpoint
-​ Control point where stop and go signals can regulate the cycle
-​ Part of the Cell Cycle Control System - cyclically operating set of molecules in the cell
that both triggers and coordinates key events in the cell cycle
Cyclins & CDKs
-​ There is a rhythmic fluctuation of the cell cycle control molecules
-​ These molecules are proteins of two kinds:
a.​ Protein Kinase - enzymes that activate or inactivate other proteins by
phosphorylating them
b.​ Cyclin - protein whose concentration cyclically fluctuates, each cyclin is
associated with a phase/period which promotes the events of the period where it
works

Protein Kinase: Phosphorylation

Cyclins & CDKs

 -​ CDK’s activity rises and falls depending on the concentration of the cyclin inside the cell
-​ Example of CDK is the MPF or Maturation-Promoting-Factor or
M-phase-Promoting-Factor which triggers the cell into M-phase (past G2 checkpoint)

CDK’s In focus: MPF

-​ Peak cyclin = Peak MPF

-​ Each MPF phosphorylates (activates) proteins to start mitosis
-​ MPF directly and indirectly activates other kinases
-​ One thing it does is phosphorylate proteins of the nuclear lamina which causes
fragmentation of the nuclear envelope, chromosome condensation, and spindle
formation
-​ When mitosis is about to end (in anaphase stage), it switches itself off by initiating the
destruction of its own cyclin.
-​ The non-cyclin part remains in the cell until it is activated again

-​ The cyclin at each level will build up and bind with the CDKs like MPF, it will form
complexes that will then trigger the phase.
-​ It will need to receive another signal (Stop/Go Sign) from a checkpoint to proceed.
Otherwise, it will not proceed
Stop and Go Signs

-​ Animal cells have a built-in stop signals at checkpoints that can be overridden by go
signals. Meaning, the default is Stop unless a Go signal overrides it.
-​ They evaluate: Did the cell complete the crucial processes before it proceeds to the next
stage after the checkpoint?
-​ 3 Major checkpoints:
-​ • G1 checkpoint
-​ • G2 checkpoint
-​ • M Checkpoint
-​ Some references also mention an S-phase checkpoint which asks:
-​ “Is the DNA full and intact?” If yes, continue to mitosis/meiosis

G1 checkpoint and G0 phase

• G1 checkpoint is the most important for a go signal

• At the end of G1 phase

• Usually leads to completion of G1, S, G2, and M-phase.

• Without the signal, the cell exits into G0 phase (Most cells are

here where they are not dividing nor preparing to divide)

• “Is the cell big enough and has proper proteins for S phase?

G2 checkpoint

• “IS the DNA intact or damaged at any part?”

• “Was the DNA replicated during S-phase?

• If there are errors, then the cell will pause and attempt to repair.

• If the error is irreparable, the cell undergoes apoptosis, where

the parts are going to be slowly destroyed and sent to the ECM

to be picked up via phagocytosis of other cells.

M checkpoint

• During the Mitosis or meiosis phase

• “Are all chromosomes (kinetochores) properly attached to the

spindle in the metaphase plate?”

• If yes to both, regulatory protein is activated.

• This leads to the separase (an enzyme) cleaving the cohesins of

the chromosome.

Signaling molecules of the Stop and Go Signals

• Animal cells in culture showed external factors (chemical and physical)

• Most cells divide in culture only if the medium contains a growth factor which is a protein
released by certain cells that stimulates other cells to divide.

• Ex: Platelet-Derived Growth Factor is released by platelets in an area of the body where there
is an injury which leads to thedivision of fibroblasts, a connective tissue with PDGF receptor

• Density-dependent Inhibition- phenomenon where crowded cells stop dividing after forming
one layer of cells on the inner surface of the container.

• Anchorage Dependence- to divide, they must be attached to something which is possible

thru the membrane proteins and cytoskeleton elements linked

• Cells without these can multiply without limits, leading to cancer.

Loss of Density-Dependent Inhibition and Anchorage Dependence

Cancer

●​ Henrieta Lack’s tumor - helps us understand why cancer cells seem immortal

• Do not stop dividing when growth factors are depleted. They either make it or trigger growth
despite its absence

• Abnormal cell cycle control system caused by a change in one or more genes (which results to
faulty proteins)

• If and when they stop dividing, they do it randomly rather than at normal checkpoints

• Cells that acquire the ability to divide indefinitely has undergone transformation

• Normal cells- 20 to 50 cell divisions before they stop, age, and die

• Many cancer cells have changed surface proteins which the immune cells detect to know
which cells to destroy.
• If it is not destroyed, it becomes a tumor

a. Benign- remain at original site

b. Malignant- genetic and cellular changes can spread to new tissues through blood & lymph
vessels (metastasis)

Curing Cancer

• Localized- surgery to remove entire tumor or high-energy radiation (damages DNA in cancer
cels since they cannot repair their own DNA)

• Metastatic- Chemotherapy (toxic to actively dividing cells)

• Taxol- drug that freezes mitotic spindle so cells cannot proceed past metaphase

• Side effects- Nausea (due to intestinal cell damage), hair loss (hair follicle damage), and
infection (immune cells death)

hello if useful to anyone, some pointers from sir cheo's study hall last week:

GENES/CHROMOSOME ANATOMY

- Chromatids are only classified as such if they are joined by cohesin. Otherwise, they are
chromosomes that aren't duplicated.

- Know the anatomy of chromosomes.

CELL CYCLE

- G1 starts organelle duplication which ends at G2.

- There is a type of cyclin for each stage of the cell cycle (G1, G1S, S, M) and if you graph their
concentrations on one graph their intersections are the cell cycle checkpoints.

- G1 cyclin persists throughout entire cycle since the cell is continuosly growing.

- Protein Kinase and CDK enzyme regulate the cell cycle at checkpoints.

- understand the fundamentals of the cell cycle.

GENETICS

- A monohybrid cross of heterozygous + homozygous will always result in a 50/50 split of

homozygous and heterozygous.

- You can use basic game theory for the probability of getting a certain gene set from a dihybrid
cross to save time.

e.g. Probability of getting PPqq from PpQq x PPqq cross

1/2 chance of getting PP from parents

1/2 chance of getting qq from parents

multiply the two: probability is 25%

Heredity and Variation

At the end of the review, you should be able to:

1.​ Describe the experiment of Gregor Mendel;
2.​ Explain the 3 laws of Mendelian Genetics; and
3.​ Explain the concepts of non-Mendelian genetics

Early Times
-​ A child would bear some resemblance especially in terms of physical appearance with
the parents.

Gregor Johann Mendel

 ●​ Austrian monk who studied heredity in plants
●​ Garden peas (Pisum sativum) because they contain both male and female
reproductive organs in the same flower

The Garden Peas

●​ The setup is self-contained and the plant is self-pollinating
●​ If he needs to, he can do cross-pollination where he removes the male organ and dust
off another male organ’s pollen to do it

Mendel’s Observations
●​ Characteristic - category of trait (Ex. Hair color)
●​ Trait - observable characteristic that is inherited (Ex. Blonde)

Example of Mendel’s Observations

●​ Tall and short plant crossed (True breeding plants- Homozygous)
●​ His predictions: 50% tall, 50% short population
●​ Reality: All offspring were tall

Rule of Unit Factors in Pairs

●​ Every individual has two “factors” that control each trait
●​ These “factors” are now known as genes in the chromosome
●​ There are two types of traits (two alleles) that might exist in the chromosome

Gene and Locus

●​ Gene - basic unit of heredity
●​ Locus (plural: loci) - Actual location of the gene on a region of a chromosome
Genome
●​ Complete set of DNA necessary to build and maintain an organism’s complete list of
structure and function

Allele
●​ Form of a gene found at a particular locus

Rule of Dominance
●​ The trait that is observed is “Dominant” while the one that disappeared is “recessive”
●​ Hence, tall is dominant while short is recessive

Dominant and Recessive

●​ As a rule, the characteristic uses the same letter
●​ The dominant trait uses capital letters while the recessive uses small letters
●​ The dominant allele is always written first
Dominant: Polydactyly

●​ Dominant is NOT equal to frequent

●​ Dominance - Presence of one copy of the gene leads to its expression
●​ Gene Frequency - how often that trait is present in the population

Law of Segregation
●​ Every individual has two types of traits (two alleles)
●​ Only one is passed on to the next generation
●​ This segregation of traits happen during the formation of sex cells (oogenesis or
spermatogenesis or sporogenesis)
●​ Hence, we can predict the trait of a set of offspring.

Segregation of Traits
Monohybrid Cross
●​ Breeding experiment that involves crossing two organisms that differ in a single trait

Punnett Square
●​ Diagram that predicts the possible outcomes of a genetic cross between two organisms

Monohybrid Cross
1.​ Identify the genotype of the parents
2.​ By the Law of Segregation, the alleles separate into single entries (letters) for each trait.
3.​ Draw a table with 2 rows and 2 columns
4.​ Write the separate alleles of one parent on top horizontally, while the other parent’s
alleles on the left side vertically
5.​ Inside the boxes, write the resulting allele combination denoted by the row and column
of the table
6.​ Count those with resulting similar phenotypes to come up with the Phenotypic ratio.
Apply the Principle of Dominance.

Try breeding BB x bb

Ratios
●​ Genotype - genetic makeup of an individual
●​ Phenotype - physical characteristic expressed given the genetic makeup

Thus, Genotypic Ratio is 4Bb

Phenotypic Ratio is 4 dominant

Law of Independent Assortment

●​ Genes for different traits are inherited independently of each other
●​ Hence, we can predict two traits at a time.
Dihybrid Cross
●​ Considers two traits at a time
●​ Will have headers with two letters

Dihybrid Cross
1.​ Identify the genotypes of the parents
2.​ For each parent, determine all possible unique combinations of alleles of the 2 different
traits. You may try using the FOIL (First, Outer, Inner, Last) Method
3.​ Draw a table with 4 rows and 4 columns
4.​ Write the possible unique combination of alleles of one parent on top horizontally, while
the other parent’s traits on the left side vertically
5.​ Inside the boxes, write the two resulting allele combinations denoted by the row and
column of the table. Alleles from the same trait must be kept together
6.​ Count those with resulting similar genotypes two come up with the Genotypic ratio
7.​ Count those with resulting similar phenotypes to come up with the Phenotypic ratio.
Apply the Principle of Dominance

Sample
●​ Eye color - B (brown) is dominant over blue (b)
●​ Dimples - Dimpled (D) is dominant over non-dimpled (d)
●​ Make the Punnett Square and determine the genotypic and phenotypic ratio of the
offspring of BBDD x BbDd

BBDD x BbDd
●​ Genotypic Ratio: 4 BBDD: 4 BBDd: 4 BbDd: 4 BbDD
●​ Phenotypic Ratio: 16 Brown-eyed and dimpled

NON MENDELIAN GENETICS

-​ Patterns of inheritance that does not follow Mendel’s Laws and Observations
Dominance
●​ Complete dominance - 2 phenotypes are seen among the genotypes
●​ Codominance - both traits that can be expressed at the same time for heterozygotes
●​ Incomplete Dominance - the traits mix into a new phenotype for heterozygotes

Codominance vs. Incomplete Dominance

So far..
●​ We have seen interactions of Allele 1 vs. Allele 2 on the same loci of a chromosome.
●​ Fighting for physical expression

Now we study…
●​ Interactions between alleles of different traits.
●​ Meaning, we look at how one characteristic and/or trait affects others

Non-Allelic Gene Interactions

●​ One gene is interacting and affecting the expression of the phenotype of another gene
Non-Allelic Gene Interactions
1.​ Epistasis (PR of 12 : 3: 1)
2.​ Pleiotropism
3.​ Complementary Gene Interaction (PR of 9 : 7)
4.​ Supplementary Gene Action (PR of 9 : 3 : 4)
5.​ Duplicate Gene Interaction (PR of 15 : 1)

Epistasis
●​ Epistatic gene - suppresses or masks the phenotypic expression of another gene at
another locus
●​ Epistatic - Gk. meaning standing up
●​ Hypostatic gene - the suppressed gene

1.​ Recessive Epistasis - presence of homozygous recessive masks the phenotype of the
other gene regardless if it is homozygous or heterozygous resulting to PR of 9 : 3 : 4.
​ ​ Ex. aa will prevent the expression of BB, Bb, or bb

ee epistatic; B/b hypostatic (Recessive)

●​ B locus codes for sa step in melanin production, B is more efficient than b
●​ Therefore, BB and Bb means black coat while bb means brown coat
●​ E locus controls deposition of melanin in coat. EE or Ee = black or brown coat
●​ ee means no deposition; yellow coat
Non-Allelic Gene Interactions (Dominant Epistasis)

2.​ Dominant Epistasis - presence of heterozygous or homozygous dominant masks the

phenotype of the other gene regardless if it is homozygous or heterozygous resulting to
PR of 12 : 3 : 1
a.​ Ex: AA and Aa will prevent the expression of BB, Bb, or bb

A_epistaticl B/b hypostatic (Epistasis: Dominant)

Pleiotropism
●​ Pleion (Gk.) - Meaning more
●​ Trepein (Gk.) - meaning influencing
●​ The gene affects different characteristics of one individual
●​ Caused by altering gene sequences

Pleiotropism: Gene Pleiotropy

●​ Aka molecular gene pleiotropy
●​ One gene = multiple features

Pleiotropism: Developmental Pleiotropy

●​ Mutation influences multiple traits
●​ Focus is on how it manifests during developmental stages

Pleiotropism: Selectional Pleiotropy

●​ focuses on the number of separate genetic fitness components affected by a gene
mutation
●​ How successful is an organism in transferring genes via sexual reproduction

Next examples are all under Pleiotropism

Mendel’s Peas
●​ White-flowered peas also had colorless seed coats and axils
 ●​ Purple-flowered peas had brown-grey seed coats and reddish axils

Frizzle gene in chickens

●​ Causes defective (curling) feathers
●​ Abnormal body temp.
●​ Higher metabolic, blood flow, and digestive rate
●​ Laid fewer eggs

Vestigial gene in Fruit fly

●​ Causes short wing for homozygous recessive
●​ Changes number of eggs
●​ Alters body parts
●​ Decreases life span

Marfan’s Syndrome
●​ Affects connective tissue (fibers that support and anchor organs/structures)
●​ Affects heart, eyes, blood vessels, skeleton
Sickle Cell Anemia
●​ severe form of the inherited blood disorder, sickle cell disease
●​ C-shaped RBC which are stiff and sticky

Moving On
Complementary Gene Interaction
●​ Gene 1 and gene 2 have an effect on a single trait and complements each other
●​ Loss of function (homozygous recessive) in either or both will result to loss of function of
both
●​ PR of 9 : 7
●​ Loss of function of either A or B, or both, will have the same result: no pigment
production. Thus A_bb, aaB_, and aabb will all be colorless, while only A_B) genotypes
will produce pigmented product

Supplementary Gene Action

●​ The dominant allele of one gene has regular phenotypic effect while the dominant allele
of another gene affects it
●​ Second gene does not produce a phenotype of its own. It is merely a supplement to
the first gene
●​ AA, Aa, aa regularly expressed but the presence of B in BB or Bb will change the
expression
●​ PR of 9 : 3 : 4

●​ CC and Cc: Colored

●​ cc: Albino
●​ Presence of AA or Aa in CC or Cc will turn the colored into agouti (gray) as the third
phenotype
Duplicate Gene Interaction
●​ The two loci have the same (redundant or duplicate) biological pathway
●​ Two genes have the same effect
●​ Thus only the homozygous recessive allele of both genes will result in a different
phenotype
●​ PR of 15 : 1

Polygenic Inheritance
●​ One trait is controlled by multiple independent genes
●​ The Polygene refers to a gene that exerts a slight effect on a phenotype along with other
genes
●​ The effect is minute that it is difficult to observe and will hence need other genes with
similar effect to make an observable phenotype
●​ Skin pigmentation: Around 60 loci contribute to this

●​ Height - Around 400 genes contribute and are influenced by the environment
 ●​ Eye color - 14 or even more genes contribute to the expression of the 9 possible eye
colors

Sex Linkage
●​ Some genes are found on the sex chromosomes (23rd pair in humans)
●​ XX for females, XY for males
●​ Males with a gene for the disease in X chromosome will readily express it compared to
females that can have another copy of the gene in X chromosome

Discovery of Sex Linkage

●​ Drosophila melanogaster was chosen for it can be easily cultivated, has short lifespan,
easy to reproduce, has clear male and female characteristics, and has many hereditary
variants
●​ Dihybrid cross was done between white-eyed male and red-eyed female
●​ Done by Thomas Hunt Morgan

●​ F1 generation was crossed

●​ Results: 1 red-eyed female : 1 white-eyed female : 1 red-eyed male : 1 white-eyed male
●​ Therefore, it is not lethal in females
●​ Also, all eye colors are possible for both sexes
●​ White-eye trait can be passed to females when F1 females are crossed with white-eyed
males
●​ Thus the eye color can be carried in the sex chromosome
Sex Linked Diseases/Disorders
●​ Color blindness is more common in males

●​ Which one is the disorder, the dominant or recessive allele?

●​ To which sex is the disease more frequent?
 ●​ Hemophilia - blood doesn’t clot in the typical way because it doesn’t have enough
blood-clotting proteins (clotting factors)
●​ Linkage - physical connection of genes that gives them tendency to stay intact and be
passed to the next gen
○​ Genes are linked if they are located in the same chromosome
●​ Crossing over - exchange of parts of the chromosome and formation of new linkages or
recombination
○​ occurrence of crossing over between two genes is decreased if they are placed
closely

Recombination or Crossing-Over

Recombinant and Parent Alleles

Linkage Types
●​ Complete - occurs when two or more characteristics are inherited and surface in two or
further generations
●​ Incomplete - genes are situated at a distance on the chromosomes