V. Genetics

Key focus of this chapter: DNA and Chromosome

This chapter focuses on DNA and Chromosome and gives concise summaries of the important things about cell division, mendelian genetics, making protein, and mutation.

A. Cell Division

1. Cell cycle

a. Controlling cell cycle

G1 checkpoint

– determines whether cell cycle goes to S phage or G0 phage, which is no dividing state.

– cell growth checkpoint

G2 checkpoint

– checkpoint before M phage.

– DNA synthesis checking point.

– controlling MPF molecule, which is to promote mitosis and composed of Cdk and cyclin.

M checkpoint

– checking mitotic spindle at metaphase.

b. Mitosis

Produces genetically identical daughter cells (2N → 2N) in somatic cell.
Occurrs for repairing tissues and growing organisms.

Cell phages		Classification	Descriptions
Interphase		G1 phase	• Cell growth • First gap • The longest phase of cell life
		S phase	• DNA synthesized • Duplicated chromatin
		G2 phase	• Cell growth and preparing for mitosis • Second gap
M Phage	Mitosis	Prophase	• Nuclear envelope disappears • DNA condenses into chromosomes • Spindle microtubule begins to form • Centrosomes move into opposite ends of the cell
		Metaphase	• Chromosomes align along the metaphase plate • Spindle fibers attach to the kinetochores
		Anaphase	• Separating and moving sister chromatids to opposite poles by spindle fibers
		Telophase	• Nuclear envelopes reappears • Chromosomes begin to be less condensed
	Cytokinesis	Cytokinesis	• Two daughter cells form • Plant cell: forms cell plate • Animal cell: forms cleavage furrow

c. Meiosis

Sexual reproduction resulting in spores or gametes.
Reducing chromosome sets from diploid to haploid (2N → N) in germ line cells.
Genetic diversity increased by independent assortment.

** Interphase in mitosis is same as in meiosis.

Meiosis I	Prophase I	• Nuclear envelope disappears • DNA condenses into chromosomes and then forms homologous chromosome pairs (tetrad) • Synapsis and crossing over of homologous chromosomes at chiasma • Spindle microtubule begins to form • Centrosomes move into opposite ends of the cell
	Metaphase I	• Pairs of homologous chromosomes line up along the metaphase plate • Spindle fibers attach to the kinetochores
	Anaphase I	• Pairs of chromosomes separate and move to opposite poles by spindle fibers.
	Telophase I & Cytokinesis	• Forming two haploid daughter cells • Plant cell: forming cell plate • Animal cell: forming cleavage furrow
Meiosis II	Prophase II	• Spindle microtubule begins to reform • Centrosomes move into opposite ends of the cell
	Metaphase II	• Chromosomes align along the metaphase plate • Spindle fibers attach to the kinetochores
	Anaphase II	• Chromosome separate and sister chromatids move to opposite poles by spindle fibers
	Telophase II & Cytokinesis	• Nuclear envelopes reappear • Chromosomes begin to be less condensed • Haploid daughter cells form • Cell plate of plant cell and cleavage furrow of animal cell

2. Cycle of sexual life

Gametes

– reproductive germ-line cells

– haploid cells (n)

– eg/ Sperm and eggs

Zygote

– fertilized egg

– diploid cell (2n)

Somatic cells

– forming body of eukaryotic species except reproductive germ-line cell

B. Population genetics

1. Hardy-Weinberg equilibrium

a. Equation

b. Condition

Large population
Isolation (no gene flow)
No mutation
Random mating
No natural selection

2. Genetic Drift

: reducing genetic variation from one generation to next generation.

a. Bottleneck effect

Sudden disasters drastically reduce the drastic size of population.

b. Founder effect

Isolated group from large population loses genetic variation and establishes new population.

3. Genotype Frequency

a. Inbreeding

Breeding between closely related animals to increase homozygotes of progeny.

b. Hybridization

Breeding between different related animals to increase variation of species and characteristics of both parents.

C. Mendelian genetics

1. Terminology

Allele

– alternative form of a gene.

– eg/ P: dominant allele, p: recessive allele

Phenotype: observable trait
Genotype: genetic constitution
Dominant allele

– determining the phenotype of organism.

– appearance of the treat from dominant homozygotes and heterozygotes.

Recessive allele

– not affecting the phenotype of organism.

-only appearance of the traits from recessive homozygotes.

Hemizygous – describing sex-linked genes such as male chromosomes (XY).
Pair of homologous chromosomes.

– same staining pattern (same length and centromere position) between two chromosomes.

Homozygous: A pair of identical alleles.
Heterozygous: A pair of different alleles.

Pair of homologous chromosomes	Homozygous	Heterozygous
	AA, aa	Aa

Law of segregation

– separating two alleles into one allele to be different gametes during gamete formation.

Law of independent assortment

– separating each pair of alleles and assorting independently of one another during gamete formation.

Testcross

– to determine the genotype of parent organism, crossing a recessive homozygous individual with the dominant phenotype of daughter organism.

– the result of all dominant phenotype is homozygous type of parent.

– the result of half dominant and half recessive phenotype is heterozygous type of parent.

2. Mendelian experiments

Classification	Figures	Features
P generation
F1 generation
F2 generation

Monohybrids

– crossing between two heterozygotes of F1 generation having a single characteristic.

– eg/ Bb × Bb → Phenotypic ratio with 3:1

Dihybrids

– crossing between two heterozygotes of F1 generation having two characteristics.

– eg/ BbDd × BbDd → Phenotypic ratio of 9:3:3:1 from F2 generation

3. Law of probability

Traits	Figures	Features and diseases
Sex-linked traits		• Passing the traits on X chromosome to offspring • Male offspring have the traits when the female parent have the gene • Female offspring have the traits when both of the parents have the gene. • Eg/ Hemophilia, color blindness
Autosomal traits		• Diseased offspring with heterozygous and homozygous recessive • Eg/ Achondroplasia dwarfism, Huntington’s disease, progeria (premature aging)
Autosomal traits		• Diseased offspring with homozygous recessive • Eg/ Sickle cell anemia, PKU disease, albinism, Galactosemia, Tay-Sachs disease

4. Pedigrees

Autosomal traits

– father has no disease but one female offspring has disease.

Dominant traits

– do not skip diseases in every generation.

Recessive traits

– both parents has no disease but at least one offspring has disease.

5. Inheritance

a. Complete dominance

Having one phenotype of F1 generation from both parental traits.
Purple flower × white flower → purple flower

b. Incomplete dominance

Having an intermediated phenotype of F1 generation from both parental traits.
Eg/ White flower × red flower → pink flower

c. Codominance

Having both phenotypes of F1 generation from both parental traits.
Eg/ roan horse (black coat × white coat → black and white coats)
Eg/ blood group (I^A, I^B, I^o), (multiple alleles or polymorphism)

Phenotype	Genotype	Antibodies
A		Anti-B
B		Anti-A
AB		None
O		Anti-A, Anti-B

d. Pleiotrophy

A single gene affects symptoms of the multiple phenotypic traits.
Eg/ Sickle-sell disease

e. Epistasis

Phenotypic expression by alternation one gene to the second gene.
Eg/ Color of mice

f. Polygenic inheritance

Phenotypic expression by quantitative variation of gene.
Eg/ Skin color

g. Penetrance

Percentage of individuals showing mutant genotype.

h. Multifactorial disorder

Disorder with genetic component from environmental effects.

i. Maternal effect

Inheritance of mitochondrial DNA from the mother.

D. Gene experiment

1. Griffith transforming experiment

a. Experiment

– 1) injection living S cells (encapsulated bacteria) into a mouse → mouse dies

– 2) injection living R cells (nonencapsulated bacteria) into a mouse → mouse lives

– 3) injection heat-killed S cells into a mouse → mouse lives

– 4) injection mixture of heat-killed S cells and living R cells into a mouse → mouse dies

b. Conclusion

The living R bacteria were converted into the pathogenic S bacteria by an unknown.

2. Avery, Macleod, Mc Carty experiment

a. Experiment

– 1) mixture heat-killed S cells, living R cells, and protease → living S cells

– 2) mixture heat-killed S cells, living R cells, and ribonuclease → living S cells

– 3) mixture heat-killed S cells, living R cells, and deoxyribonuclease → no living S cells

b. Conclusion

DNA is the transforming factor.

E. Chromosomal basic

1. Chromosomes in humans

46 chromosomes in diploid cells (2n).
23 chromosomes in haploid gametes (n).
2 sex chromosomes (X and Y) and 44 autosomes.

2. Chromosome appearances

Classification	Features
Metacentric	Location of centromere at middle of chromosome
Acrocentric	Location of centromere at close to end of chromosome
Telocentric	Location of centromere at end of chromosome

3. Level of chromosomal organization

Histone: DNA packing molecules composed of protein.

4. Linked genes

: genes on the same chromosome are inherited jointly in crossing over.

Measuring the gap between two linked genes by probability of crossing over.
Increased probability of crossing over with greater the gap between two linked genes.
Linkage map

5. Sex-linked genes

: genes on X or Y chromosomes.

Sex-linked recessive traits

– hemophilia

– color blindness

Barr body: an inactivated x-chromosome

6. Chromosomal alteration

a. Changing chromosome number

Nondisjunction

– separation failure of pairs of homologous chromosomes in meiosis I or chromosomes in meiosis II.

Aneuploidy

: abnormal number of chromosomes from the nondisdunction of meiosis I or II.

– monosomic (n –1): Presence of one chromosome

– trisomic (n+1): Presence of three chromosomes

Polyploid

: more than two sets of chromosomes.

– triploidy (3n)

– tetraploid (4n)

b. Changing chromosomal structures

Translocation

– breakage and rearrangement of chromosome.

Deletion

– lost chromosomal segment.

Duplication

– repeating chromosomal segment.

Inversion

– reverse attachment of chromosomal segment.

7. Human disorders

a. Down syndrome

Nondisjunction of chromosome 21 (Trisomy 21)
47 chromosomes

b. Klinefelter syndrome

Nondisjunction of X chromosome
Sterile male with XXY chromosomes
Female body characteristics
47 chromosomes

c. Turner syndrome

Nondisjunction of X chromosome
Sterile female having only one X chromosome
Monosomy of sex chromosome
45 chromosomes

F. DNA replication

1. DNA structure

Rosalind Franklin made X-ray diffraction photograph.
James Watson and Francis Crick corrected DNA model of double helix structure.
DNA backbone: carbon sugars bound to phosphate groups.
Purine: A (adenine), G (guanine).
Pyrimidine: C (cytosine), T (thymine).
Two hydrogen bonds between A and T, three hydrogen bonds between G and C.
Molecules containing G and C have a higher melting point than those containing A and T.

2. Chargaff’s rules

A+G = C +T
Eg/ A = 30%, G = 20%, C = 20%, T = 30%

3. Semiconservative model

Parents strands separate and give template. strands to each daughter
Each daughter strand contains one template strand and new strands.
1/2 radioactivity of daughter strands from the parents.

4. DNA replication

DNA replication	RNA replication
A ⇔ T G ⇔ C	A ⇔U G ⇔ C

a. Origins of replication

Replication fork

– Y shaped site by helicases.

– places of elongation of new strand DNA.

b. Elongation

Leading strand

– DNA Pol III elongates continuously new strand of DNA from 5´ to 3´.

– same direction with movement of replication fork.

Lagging strand (Okazaki fragments)

– DNA Pol III creates short segments of new DNA from 5´ to 3´.

– opposite direction against movement of replication fork.

– overall direction of lagging strand is from 3´ to 5´.

c. Enzymes for DNA synthesis

Topoisomerase

– relieving the strain of tighter twisting from untwisting of parental DNA.

Helicase: Separating the parental double strands of DNA
Single-strand binding protein

– preventing the unwound parental strands of DNA.

Primase

– synthesizing short segments of RNA primer which is nucleotide chain for starting point of DNA synthesis and putting down the RNA primer on new strands of DNA.

DNA polymerase

– DNA Pol III: Synthesizing new DNA nucleotides.

– DNA Pol I: removing RNA primer and replacing with DNA.

– proof reading (DNA error correction).

DNA ligase

– joining the ends of new strand of DNA.

Telomerase

– adding TTAGGG nucleotides to the end of DNA in order to prevent eroding DNA strands from DNA replication.

d. Repairing DNA

G. Making protein

1. Central dogma

2. Transcription

a. Initiation

① Transcription factors bind to the TATA box of promoter.

② RNA polymerase binds to promoter along with the transcription factors.

③ RNA polymerase binding on DNA begins to synthesize pre-mRNA.

b. Elongation

RNA Polymerase elongates pre-mRNA from 5´ to 3´

c. Termination

Finishing pre-mRNA transcript

3. RNA processing

a. Modifying of pre-mRNA ends

Adding 5´cap and poly-A tail to pre-mRNA ends

b. RNA splicing

: spliceosome removes introns from pre-mRNA and splices exons together to make mRNA.

Introns: noncoding segments of nucleic acid
Exons: coding segments of nucleic acid
Spliceosome: snRNPs + other proteins

4. Translation

a. Codons and anticodons

Codons: triplet nucleotides at mRNA and translated into amino acids

– start codon: AUG (met)

– stop codon: UAA, UAG, UGA

Anticodons: triplet nucleotides at the end of tRNA and complementary on codon
Wobble: only necessary at the first two codons when tRNA meet with mRNA (degeneration of genetic code)

b. tRNA

Features

– hydrogen bonds with short double stranded RNA.

– presence of unusual bases: methyliosine, pseudoridine, 4-thiouridine.

Aminoacyl-tRNA synthetase binds an amino acid to 3´ end of tRNA

c. Ribosomes

: making polypeptide after reading m-RNA from from 5´ end to 3´ end and requiring energy (GTP → GDP).

A site

– aminoacyl-tRNA binding site.

P site

– peptide bond formation.

– translocation of peptide bond.

E site

– exit of tRNA site.

H. Mutation

1. Point mutation

: substitution of one nucleotide molecule.

Missense: result of a different amino acid by altering codon
Nonsense: result of stop codon
Silent: result of same amino acid although altering codon

2. Frame shift

: insertion or deletion of a single nucleotide molecule.

Causing serious genetic diseases
Missing or insertion

3. Cancer

Oncogenes: genes leading to cancer.
A mutation in a gene of somatic cell induces to tumor.

I. Gene technology

1. Polymerase chain reaction (PCR)

Quickly copy and amplify an original double strand of DNA.
Useful for critical forensic analysis.

2. X-ray diffraction

Method to know the three-dimensional molecular structure.
X-ray crystallography.

3. DNA fingerprint

Identification of an individual’s DNA by their DNA profiles.

4. Transgenic organism

Genetically altered organism from another organism.