Cell Division

Introduction
 Chromatin - a network of DNA

o Turns into chromosomes when cell division is about to take place

o DNA has to duplicate

 Chromosomes - condensed chromatin

 Chromatids and centromeres

o Sister chromatids

 Cell division - when a single cell divides into two identical cells

 Cell cycle

o
1. Interphase - rest phase

 G1 = growth

 S = growth and DNA synthesis

 G2 = growth and final preparation for division

2. Mitotic Phase - division takes place; PMAT; aka Karyokinesis

 Prophase, Metaphase, Anaphase, Telophase

 cell doesn’t change shape during mitosis

 → Cytokinesis

 2 daughter cells

 Back to interphase

Mitosis (equational division)

 Asexual

 Phase in which the nucleus divides to form two nuclei, each containing a

complete set of the cell’s chromosomes

o Prophase - chromosomes become visible and spindles form; nuclear

envelope breaks

o Metaphase - chromosomes line up along the equator and spindles connect to

the centromere

o Anaphase - sister chromatids separate at the centromere and are pulled to

opposite poles; microtubules contract

 Mitotic spindles
o Telophase - nuclear envelope forms, chromosomes uncoil and spindles

dissolved

 Cytokinesis - process where the cytoplasm divides into two

 One original cell and one exact copy

 Plant cell - cell plate appears in center

 In animal cells, it starts at the periphery and ends at the center

 In plant cells, it starts at the center and moves to the periphery

Meiosis (reductional division)

 Meiosis I - PI, MI, AI, TI

 Meiosis II - PII, MII, AII, TII

 homologous - a pair of chromosomes

o similar shapes, size and arrangement of genes

o maternal and paternal chromosomes

 crossing over - mutual exchange of genes takes place

o genetic variation occurs

o occurs in prophase I of meiosis

o chiasmata - point where the chromosomes attach

o recombinant chromosomes

 haploid cells cannot undergo meiosis but diploid cell can

 both haploid and diploid can undergo mitosis

 Mitosis Interphase
Embryonic development Growth Cell growthDNA synthesis Resting
Tissue repair Asexual reproduction but active Organelles duplicate

History and Discovery of the Structure and

Role of DNA
 1869 - Friedrich Miescher was a Swiss chemist and the first to identify DNA

as a unique molecule

 1914 - Robert Feulgen (German chemist); staining technique

o More DNA = more staining

o All cells in an organism have the same amount of DNA except gametes

 Fred Griffith - demonstrated that bacteria could be transformed from one

strain to another by transferring genetic factor from one organism to another

o Living S (smooth) cells = mouse is dead(strain is protected by a capsule from

the mouse’s defenses)

o Living R cells = alive

o Heat killed S cells = alive

o Heat killed S cells + Living R cells = dead

o conclusion was that the bacteria had incorporated heredity factor from a

source and in doing so expressed a new smooth trait

 Avery, MacLeod and McCarty examined various molecules found in S-strain

Pneumococcus cells to prove that DNA was responsible for the

transformation of the bacterial cells

o When various isolated chemical components of the S-strain pneumococcus

cells were mixed with the R-strain pneumococcus cells, it was shown that the

DNA from the S-strain cells that caused transformation

 Alfred Hershey and Martha Chase

o Demonstrated that genetic material is DNA by using viruses that infect

bacteria

o Phage used in experiment = DNA molecule surrounded by a protein coat

o Part 1

 Phages grown with sulfur (S 35) labeled amino acids → radioactive protein

coat

 No radioactive DNA

 Phages infected bacteria

 Phages produced in these cells contained no radioactivity

 Separate phages outside the bacteria from the cells using a blender

 Centrifuge the mixture so bacteria form a pellet at the bottom of the test

tube

o Part 2

 Phages grown with phosphorus (P 32) radioactive deoxyribonucleotides →

radioactive DNA

 Radioactive DNA present in bacteria

o This demonstrated that the DNA not protein carries the genetic information

 Chargaff’s rule

o Found the percentage of various nucleotides in genome

o Rules

 A+G = C+T = 50%

 Percentages of nucleotide vary for different species

 Rosalind Franklin - used x-ray crystallography to determine that DNA was

double stranded, a helix, phosphates were on the outside and three

distances (2 nm, 0.34 nm and 3.4 nm) showed up in a pattern over and over

again in the diffraction pattern

 James Watson and Francis Crick

o Determined that the sugar and phosphates were on the outside

o Determined that the nitrogenous bases were forming the rungs of the ladder

o Two purines are too wide to overlap and two pyrimidines are too far apart to

form the hydrogen bonds

o A purine and a pyrimidine is just right

Structure of DNA
 Double helix - two chains of atoms twisted around each other

o Atoms are held together with covalent bonds

o Two strands in the spiral are held together with hydrogen bonds

 Hydrogen bonds are weaker → important when unzipping

 DNA is a polynucleotide

o Each nucleotide is made of a nitrogen base, a sugar and a phosphate group

 Sugar = deoxyribose

o Base pairs - A+T or G+C

 Held together with hydrogen bonds

 The Power of DNA

 DNA-DNA hybridization

o The closer the two species are, the fewer mispairings there are in

hybridization

 Human Genome Project - only 5% of DNA is actually useful

 Lynn Margulis - extracted and compared DNA from organelles and confirm its

similarity to the DNA in groups of wild, free-living bacteria and cyanobacteria

o Ideas of eukaryotic cells gained acceptance as a result of DNA analysis

DNA Replication
 Helicase - enzyme that breaks hydrogen bonds

o Replication fork - where replication begins

 Leading strand - continuous synthesis

 Lagging strand - not continuous; okazaki fragments

o 5’ → 3’

 SSBP - single stranded binding protein; binds to both strands to keep them

apart

 RNA primase - synthesizes primer for replication to start

 DNA polymerase - adds nucleotides to the parent DNA strand

o A-T and G-C

 Complementary base pairings

o Strands are antiparallel

 DNA ligase - joins the two DNA strands together by forming a phosphodiester

bond
 Protein Synthesis
 Essential amino acids - our body can’t synthesize them

o Non essential = can synthesize

o 20 amino acids build up proteins

 Transcription - happens in the nucleus

o Transcription unit - length of DNA to be copied

o Transcribe DNA

o Only one strand is formed at a time from a template to avoid complication

 Copied strand = antisense strand

 Not copied strand = sense strand

o If both strands are used, various proteins will form at the same time

(hypothetically)

o RNA polymerase - binds to DNA at the TATA box to unzip the double helix

 Read the DNA bases and helps the RNA versions find a match

 RNA polymerase adds on in the 3’ → 5’ to create a strand that is 5’ → 3’

o mRNA - messenger RNA

 Leaves nucleus through nuclear pores and moves to the cytoplasm and

attaches to a ribosome

 Uracil instead of Thymine

 rRNA is the ribosome

 Translation - happens in the cytoplasm/ribosome

o Codon - thee template bases on mRNA

o Anticodon - three template bases on tRNA

o tRNA decodes and brings the amino acids from the cytoplasm and sequences

them according to the mRNA codons

 Polypeptide chain forms → protein

 tRNA leaves

Mutations
 Mutation - a change in the DNA base sequence

o Substitution - one replaced by another

o Insertion - addition of an extra base

o Deletion - removal

o Inversion - change in sequence

o Duplication - one segment is repeated

 When a mutation occurs, the type of protein formed changes

 Point mutation - change occurs for one base pair only

o Substitution

 Frameshift mutation - protein changes from the point of insertion, deletion,

duplication or inversion

o Entire frame shifts from that point

 Silent mutations - changes in the bases that don’t cause mutation in

phenotype/mutation/amino acid

o This happens when there are multiple ways to code the same amino acid ** \

n **

Mendel’s Laws
 Somatic cells - non-reproductive cells
o Diploids - 2 sets of chromosomes

o Reproductive cells are haploids

 Gregor Johann Mendel - first to explain inheritance patterns

 Pea plant (pisum sativum) complete dominance experiments

o Identified 7 different visible characteristics that are of contrasting strains

o Self and cross pollinated the plants

 Plant is bisexual so both self and cross pollination can take place

 This can occur in a short period of time

o Parental (P) and filial (F1 and F2) generations

o Self pollinate plants for a few generations to ensure purity of plants

o Cross pollinate a tall plant and a short plant

 Remove the anthers from the plant to be pollinated

 Tall x Dwarf \n TT x tt \n Tt → F1 generation = tall

o Self pollinate F1 generation

 Tt x Tt

 Punnett Square → TT, Tt, Tt, tt

 Phenotype and genotype ratios

o Monohybrid Cross:

 In this case, we are taking the alleles for the seed shape of the pea plant,

where R (round) is the dominant allele and r (wrinkled) is the recessive gene.

 Breeding experiment between P generation (parent generation).

 P generation parent are homozygous with different alleles for the same trait.
 The possible gametes for the first parental generation are R and r

(homozygous dominant parent will have R, R and homozygous recessive

parent will have r, r).

 The first filial generation or F1 will all be daughters that will be Heterozygous

Dominant with gametes R, r.

 After this, the first generation are all self-pollinated. Here the possible

gametes are (R. r) (R, r). To find the exact ratios we use the Punnett Square.

From the Punnett Square we can see that the Phenotypic Ratio is 3: 1. While

the genotypic ratio is 1:2:1.

 Test cross is the crossing of an individual with a recessive individual in order

to build the genotype of the dominant individual.

 In a heterozygous individual the dominance is called Complete Dominance as

recessive allele is completely suppressed by the dominant allele.

 Incomplete dominance is when two homozygous plant with two dominant

genes are crossed and a new allele is formed that is a mix of the two

dominant.

 All F2 generations of incomplete dominance have genotypic and phenotypic

ratio.
 Mendel could only explain complete dominance and not incomplete

dominance.

 Co-dominance is two homozygous individuals with dominant alleles have an

offspring with alleles being equally dominant without interference.

o Di-hybrid cross:

 It is a cross with two different traits.

 In this example, we are taking the seed colour and seed shape. That is either

yellow/round and either green/wrinkled. In this Round and Yellow are the

dominant alleles.

 Again, both the parents in the parent generation are either homozygous

dominant or homozygous recessive. That is YY RR and yy rr.

 The possible gametes for the first parent in the first generation are (Y R) and

(r y)

 Thus, the first generation filial offspring are all R r y Y.

 We then self-pollinate the F1 generation.

 Here the possible gametes for one of the parents- RY, Ry, rY, ry.

 And the same for the second parent.

 We make a Punnett Square grid again and the following are the ratios-

phenotypic ratio is 9:3:3:1 :: Round Yellow: Round Green: Wrinkled Yellow:

Wrinkled Green.
 Recombinants that are formed after the crossing like Round Green and

Wrinkled Yellow.

o Chromosomes are either autosomes or allosomes

o Allosomes are the sex chromosomes.

o There are 22 pairs of autosomes and one pair of allosomes.

o Genes of autosomes are autosomal genes and genes of allosomes are sex-

linked genes.

o Genes of Y-chromosome are Y-linked genes

o Y-linked are inherited from male to male only.

o In females, the 23rd pair of the sex-linked pair is XX and in males it is XY.

o Therefore, the sex determining is the Y chromosome and whether the males

pass it on.

 Key terms:

o Allele - different versions of a gene

o Gene - a segment of DNA which defines a certain trait

o Homozygotes - same alleles for the same trait

o Heterozygotes - different alleles (identical

o Dominant - whichever trait is more possible/expressive

 Represented by the capital letter of the trait

o Recessive - whichever trait is less likely to occur

 Represented by the lower case letter of the trait

o Phenotype - external/visible characteristics

o Genotype - genetic constitution/composition

 Possibilities/gene combinations

 Law of dominance - the phenotype is that of the dominant gene/allele

 If a plant self-pollinates and you get the same traits, it is homozygous

 If a plant self-pollinates and you get varying traits, it is heterozygous

 Test cross - cross tall plants with dwarf plants to see the nature of the

offsprings; it is used to find out whether the parent if homozygous or

heterozygous

o Determine the genotype of the dominant parent

o If all offsprings are found to be of one type, then the dominant parent is

homozygous

o If the offspring produced are both types in 1:1 ratio, the the dominant parent

is heterozygous

o If some are dwarf, then the parent plant is heterozygous

 Back cross - individual is crossed with either of the parents

 Incomplete dominance

o Ex: Andalusian fowl

 Black and white chickens exist

 If a white chicken breeds with a black chicken, you get a gray chicken

 WW + BB → WB = gray
o Ex: Mirabilis Jalapa (4 o’clock plant)

 Red flower and white flower = pink flower

 RR + WW → RW = pink

 Codominance - both are equally dominant

o Ex: blood groups

 A is dominant over O → IaIa or IaIo

 B is dominant over O → IbIb or IbIo

 A and B are equally dominant → IaIb

 Ex: IaIa + IbIb → IaIb (codominance)

 O → IoIo

 Sex-linked inheritance - gene is linked to the 23rd chromosome

o More likely to affect maleS

Pedigree Charts
 A pedigree chart is a flow chart that shows the relationship within a family

over several generations.

 Offspring are shown in order of birth from left to right.

 Generations are labelled with Roman Numerals

 A person that is not affected but passes it onto their offspring are called

carriers only applicable in recessive disorders.

 Autosomal Dominant - there is an altered autosomal gene on one of the 22

autosomes and someone who carriers this gene is affected by the disorder

o If the person has offspring there is a ½ chance that they pass on the disorder

even if they are female or male.

o If both parents are affected but the offspring is unaffected, the trait must be

dominant

o You will be affected if you have a A allele.

o Those that are affected can be homozygous or heterozygous.

 Autosomal Recessive

o In this the person is darkened if he/she is recessive gene.

o They have to be homozygous or AA

 X-linked Dominant

o Affected female- XAXA or XAXa

o Unaffected female- XaXa

o Affected Male- XAY

o Unaffected Male- XaY.,

o An affected father will have all affected daughters.

o To find the genotype of the mother look at the sons.

 X-linked Recessive

o Affected mother all sons should be affected. ‘

o Affected female- XaXa

o Unaffected female- XAXA or XAXa , in the latter case the female is a carrier

o Affected Male- XaY

o Unaffected Male- XAY

o To find the genotype of father look at the females and to find mother look at

the males

Genetic Disorders
 Caused by the passing down and inheritance of defective genes

 Mutation - a change in the sequence of bases in DNA

 Cystic fibrosis
o Excess secretion of mucus

o Protein channels are dysfunctional and don’t allow substances to pass

through

o CFTR gene codes for a protein which balances the salt levels in either side of

cells in lungs

o If a defective variation of the gene is present → blockages in some parts of

the body

 Trouble in breathing

 Blockage in parts of digestive food that can’t be absorbed

 Blockage in vas deferens → infertility

o Life expectancy = 30-40 years

 Huntington’s disease

o Progressive brain disorder

o Causes uncontrolled movements, emotional problems and loss of cognition

 Involuntary jerking, muscle problems, slow eye movement, impaired gait,

difficulty with speech production

 Difficulty organizing, lack of impulse controls, lack of awareness, slow

processing, difficulty learning new information

 Sadness and irritability, insomnia, fatigue, and frequent thoughts of death

o Usually develops between the ages of 30 and 50

o Caused by the huntingtin gene which is attached to the 4th chromosome

 Produces an important brain protein called huntingtin which is needed by

neurons in the brain and for the body’s development before birth
 When faulty → repeats genetic sequences too many times → damages

neurons in certain areas of the brain

 Haemophilia (bleeder’s disease)

o Inherited bleeding disorders where blood doesn’t clot properly

o Very rare in females

o Bleeding episodes may occur spontaneously

 Lots of internal bleeding

 Nosebleeds take long time to stop, bleeding gums, skin bruises easily, pain

and stiffness around joints

o Haemophilia A - reduced clotting factor VIII

o Haemophilia B - reduced clotting factor IX

o X-linked recessive pattern

o Mutations of the F8 or F9 gene lead to the production of an abnormal amount

of coagulation factor VIII or IX or reduce the amount of one of these proteins

 The altered or missing protein cannot effectively participate in the blood

clotting process → proper blood clots cannot form

 Down Syndrome

o Individual has an extra copy of the 21st chromosome (3 copies instead of 2)

 Extra genetic material → alters course of development

o Low muscle tone, small stature, upward slant to the eyes, single deep crease

across the palm

o Types
 Trisomy 21 (nondisjunction) - results in an embryo with three copies of

chromosome 21 instead of the usual two

 Accounts for 95% of cases

 Extra chromosome is replicated in every cell of the body

 Translocation

 4% of cases

 Total number of chromosomes is still 46

 An additional full or partial copy of chromosome 21 attaches to another

chromosome, usually chromosome 14

 Mosaicism

 1% of cases

 Mixture of two types of cells - some containing 46 chromosomes and some

containing 47

 Ones with 47 contain one extra chromosome 21

 Sickle Cell Anemia

o An inherited form of anemia

o Red blood cells become rigid and stockey and are shaped like crescent

moons

 Irregularly shaped cells get stuck in blood vessels

 Slow blood and oxygen flow throughout body

o Sickle cells usually die in 10 to 20 days rather than the usual 120 days

 Leads to shortage of RBCs → fatigue due to lack of oxygen

o Block of blood flow and lead to body pains

 Painful swelling of hands and feet

o Sickle cells can damage an organ that fights infection and leave the person

more vulnerable to infection

o Delayed growth due to lack of oxygen and nutrient supply

o Vision problems if the blood vessels that supply the eyes are plugged with

sickle cells → retina damage

o Caused by mutations in the HBB gene

 Abnormal haemoglobin called haemoglobin S

 Causes rigid, non-liquid protein strands to form within the red blood cell

 Distorts RBCs into a sickle shape

o Autosomal recessive

 Alkaptonuria

o HGD (homogentisic dioxygenase) gene provides instructions for making an

enzyme called homogentisate oxidase

 Breaks down homogentisic acid

 Faulty HGD gene → body can’t produce enough of homogentisate oxidase →

build up of homogentisic acid

o Build up causes bones and cartilage to become discolored and brittle →

osteoarthritis

 Urine turns dark brown or black when exposed to air

 Black earwax

 Dark sweats stains

 Blue speckled discoloration of skin particularly around sweat glands

 Arthritis

o Autosomal recessive

 Color blindness

o X-linked recessive