exam 3

    All you need to know about Chapters 10-13 for Exam 3

. Bacteria, with no nucleus or sexual cycle, reproduce clonally and divide by binary fission

. Bacteria’s circular chromosome starts replication at origin, proceeds bidirectionally to end

. Bacteria’s new chromosomes move to opposite ends and FtsZ protein creates middle septum (septation ), allowing the cell to divide into two identical daughter cells, each containing a complete copy of the original chromosome. This process ensures genetic consistency and is a key characteristic of prokaryotic organisms.

. FtsZ protein (found in most prokaryotes), similar to eukaryotic tubulin, forms a ring and contracts radially to pinch cell in 2

. Eukaryotic: 10-50 chromosomes in their body (somatic) cells. Humans have 46 (23 homologue pairs)

. The particular array of chromosomes (size, staining, etc.) in an individual is his karyotype

.  Humans are diploid (2n): 2 sets = 46 total chromosomes. One set of chromosomes is haploid (n) = 23

.  Chromosomes composed of chromatin = 40% DNA + 60% protein. RNA is present because chromosomes are the site for RNA synthesis

. DNA: single chromosome, 140 million nucleotides, made of DNA (- charge) & histone proteins (+charge)

• Have a bead like structure called nucleosomes, which consist of DNA wrapped around histone proteins, facilitating the compact packing of DNA within the nucleus.

. 4 primary histones (H2A, H2B, H3, H4) create 2 core histones to form an octamer, each histone has 147 bp DNA coiled 1.7 turns around 8 histones & 20-80 bp linker

. Eukaryotic organization: DNA->Nucleosome->beads on string->TADs->compartments->territories

. Topological Associated Domains (TADs): loops of DNA (nucleosomes) held by CTCF & cohesin proteins

. Organization of DNA-binding proteins CTCF & cohesin affect gene expression (activation or repression)

. Domains with different set-up of compartments & TADs are hetero- (silent) & eu-chromatin (active)

. Through cell cycle, x-shaped chromosomes compact on protein scaffold: TADs disappear in prophase

. SMC proteins (Structural Maintenance of Chromosome) interact with DNA, condensins replace cohesins

. ATP needed for DNA loops in nucleosomes. Interactions of histones and nucleosomes makes “liquid DNA”

. Replication makes 2 DNAs (sister chromatids) held by cohesins around the kinetochore protein

 . Eukaryotic cell cycle has Interphase [G1(growth), S (DNA replication), G2 (organelles replicate)], M & C

• G1 phase: This is the first checkpoint where the cell assesses its size, nutrient availability, and DNA integrity before committing to division.

• S phase: is the phase in which cell synthesizes a replica of the genome

• G2 phase: This checkpoint ensures that the cell has successfully replicated its DNA and is ready for mitosis, checking for DNA damage and making sure all proteins required for cell division are present. ( G1, S and G2 work together to constitute interphase and ensure that the cell is adequately prepared for the subsequent stages of the cell cycle, ultimately leading to successful mitosis.)

• M phase: During this phase, the cell undergoes mitosis, where the replicated chromosomes are separated and distributed into two daughter cells, followed by cytokinesis, which completes the cell division process.

• Cytokinesis is the final step of the M phase, where the cytoplasm divides, resulting in two distinct daughter cells, each with its own nucleus and a complete set of chromosomes.

. Centromere (one per chromatid) is point of constriction, kinetochore is site of microtubule attachment

. Mitosis (M) has prophase, prometaphase, metaphase, anaphase and telophase

. Prophase: chromosomes visible, centrioles move to poles and form spindle, nuclear envelope breaks

. Prometaphase: chromosomes attach to microtubules at kinetochores and move to equator of cell

. Metaphase: chromosomes align at metaphase plate (future axis of cell division), centrioles have Aster

. Anaphase: centromeres split, cohesins are removed and sister chromatids are pulled to opposite poles

. Telophase: spindle disassembles, nuclear envelope forms on both chromatids, nucleolus reappears

. Cytokinesis (C): constriction of actin creates cleavage furrow (animals), plate forms in plants

. Two irreversible steps in cell cycle: replication of DNA and separation of sister chromatids

. Cell cycle can be stop at checkpoints, check for accuracy and halted if there are errors

. 3 checkpoints: G1/S (decision to divide), G2M (mitosis), late metaphase (spindle proper attachment)

. Control Factors: MPF (maturation-promoting factor) induces division through phosphorylation

. MPF is cyclin plus a cyclin dependent kinase (cdk). Cdks are drivers of the cell cycle via phosphorylation

. Anaphase promoting factor (APC/C or cyclosome triggers anaphase itself

. Multiple Cdks control the cycle in eukaryotes as opposed to one in yeast

. Growth factors can override cellular controls that otherwise inhibit cell division

. Platelet-derived growth factor (PDGF) is an RTK that initiates a MAP cascade to stimulate cell division

. Cancer, uncontrolled growth of cells caused by mutation of tumor-suppressor genes & proto-oncogenes

. Proto-oncogenes are genes that become oncogenes when mutated. Only one is needed to cause cancer

. p53 are tumor suppressor genes that must lose function for the cancerous phenotype to develop

. p53 monitors integrity of DNA, if DNA is damaged division is halted, if major, p53 directs cell to kill itself

. Sexual life cycle: composed of meiosis and fertilization. Somatic cells are diploid, gametes are haploid

. Diploid cells carry chromosomes from 2 parents. Fertilization produces a diploid zygote

. Sexual reproduction involves meiosis (diploid ->haploid, >>in animals) and fertilization (haploid -> diploid

. Single -cell diploid zygote undergoes mitosis to produce diploid somatic cells

. Some diploid cells undergo meiosis to produce haploid gametes also called germ-line cells

. Meiosis has 2 rounds of division I and II, each with prophase, metaphase, anaphase and telophase

Division I (reduction division) gives daughter cells with one homolog. Division II separates sister chromatids

. Sister chromatids are identical copies of a single chromosome

. Homologues are pair of chromosomes similar in size, shape and gene order but # versions of those genes

. Association of homologous chromosome (Synapsis) in prophase I forms synaptonemal complex (SC)

. SC= chromatin-attached-lateral elements (LE) bound to central elements (CE) by transverse filaments (TF)

. Meiotic cells have interphase (G1, S, & G2) followed by meiosis I and meiosis II

. Prophase I: nuclear envelope gone, chromosomes (2 sister chromatids) visible, sites of crossing over form

. Genetic recombination between no-sister chromatids takes place at sites called chiasmata

. Metaphase I: locked homologues separately attach microtubules to opposite poles at metaphase plate

. Anaphase I: microtubules shorten, chiasmata break, homologues (haploids) move to opposite poles

. Telophase I: nuclear envelops reform, non-identical chromosomes separate, cytokinesis may or not occur

. Meiosis II: resembles a mitotic division

. Prophase II: shorter than prophase I, spindle forms in each cell, nuclear envelope breaks down

. Metaphase II: chromosomes align at metaphase plate, kinetochore microtubules attach to poles

. Anaphase II: kinetochore microtubules shorten, non-homologous sister chromatids pulled to poles

. Telophase II: nuclear membrane reform. After cytokinesis, four haploid cells result

. In animals the four cells develop into gametes. In plants, fungi they divide mitotically then ++gametes

.  Meiosis errors: Nondisjunction failure to move to opposite poles. Aneuploid gametes + chromosomes

. Meiosis: cross over, no DNA synthesis, chromatids joined at centromere, kinetochores attach same pole

. Mitosis: homologues do not pair, kinetochores remain separate and microtubules attach to both

. Homologous pairing is specific to meiosis and centromeres of sister chromatids remain connected

. Sister kinetochores attach to the same pole during meiosis I in contrast to mitosis and meiosis II

. Cyclin B is lost between mitotic divisions, but not between meiotic divisions

.  Meiosis produces cells that are not identical, essential for evolution

. Sexually reproducing populations have greater genetic variation than asexually reproducing ones

. Allele = one of several forms of a gene obtained by mutation & found at same place on a chromosome

. Homozygous = 2 identical alleles. Heterozygous = different alleles for a particular trait.

. Dominant allele = expressed. Recessive allele = hidden by dominant allele

. Genotype = individual’s complete set of alleles. Phenotype = individual’s physical appearance

. Pea plants are optimal: produce hybrids, many varieties, easy to grow, can self-fertilize or cross fertilize

. Mendel’s method; 1) made true-breeding strains of a trait 2) cross fertilize true-breeding strains

. 3) allow hybrid offspring to self-fertilize for several generations and count number showing each trait

. Monohybrid cross: 2 variations of a single trait. Mendel produced true-breeding strains for 7 traits

. True breeding = any cross will result in same phenotype so the organism is homozygous for every gene

. A true-breeding purple plant crossed with itself will always produce offspring that are purple as well

. Mendel’s 7 traits: flower & seed colors, seed texture, pod color, pod shape, flower position, plant height

. F1 generation is cross of true-breeding strains resembling same parent, referred as dominant

. F2 generation: self fertilization of F1 plants, recessive trait appeared in some F2 plants in ratio 1:2:1(3:1)

. 1:2:1 = 1 true-breeding dominant, 2 not-true-breeding dominant and 1 true-breeding recessive plant

. Mendel’s 5-elements: 1) parents transmit discrete factors (genes).

2) each individual gets 1 copy from each parent

3) not all copies of a gene are identical

4) alleles remain discrete (no blending)

5) presence of alleles does not guarantee expression

. Principle of segregation: 2 alleles segregated in gamete formation rejoin at random during fertilization

. Physical basis for allele segregation is the movement of chromosomes during meiosis

. Punnett square, a square that is used to predict the genotypes of a cross or breeding experiment

. Punnett square: label column and row with one parent genotype. Label each square, column letter first

. Dihybrid cross: 2 variations of 2 traits in single cross. F1 generation has dominant phenotypes for both

. F2 generation shows all 4 phenotypes in a set ratio: 9:3:3:1

. Principle of independent assortment: during meiosis, alleles of different genes assort independently

. Segregation of different alleles pairs is independent: seed shape is independent of seed color

. Testcross is used to determine the genotype of an individual with unknown phenotype based on ratio

. Rule of addition: probability of 2 mutually exclusive events occurring is = sum of individual probabilities

. Pp x Pp, probability of producing Pp offspring is = 1/4 + 1/4 = 1/2

. Rule of multiplication: probability of 2 independent events both occurring is product of each probability

. Pp x Pp, probability of producing pp offspring is = half from father x half from mother = 1/2 + 1/2 = ¼

. Dihybrid probabilities (prob) are based on monohybrid probabilities

. Wrinkled seed (rr) prob. = ¼, green seed (yy) prob. = ¼. Wrinkled green prob. = 1/4x1/4 = 1/16

. Mendel’s model of single trait to single gene of 2 alleles with clear dominant/recessive ratio is not real

. Environment affects phenotype àPhenotypic plasticity = different phenotypes, same genotype

. An allele produces an enzyme that allows pigment production only at T< 30^Oc in Siamese cats

. Many traits show continuous variation = quantitative traits. Phenotype = sum of multiple genes

. Broad sense heritability (H²) is the fraction of phenotypic variation due to genetic variation

. Narrow sense heritability (h²) is the fraction of phenotypic variation due to additive variance of a trait

. Height is a quantitative trait, the greater h² for a trait, the more offspring resemble their parents

. Pleiotropy refers to an allele that has more than one effect on the phenotype

. Pleiotropic effects are difficult to predict because a gene affecting one trait does other functions.

. Incomplete dominance, heterozygote is intermediate in phenotype between the 2 homozygotes

. Incomplete dominance: Red flowers x white flowers = pink flowers, F1 generation

. Incomplete dominance: self-crossed of F1 gives Mendelian progeny: 1 red: 2 pink: 1 white

. Codominance, heterozygote shows phenotypes of both homozygotes: type AB blood

.  May be more than two alleles for a gene in a population. Three alleles determine blood type

. Human ABO group shows multiple alleles, 3 for the I gene (I^A, I^B and i)

. Human ABO group shows codominance, I^A and I^B are dominant to i but codominant to each other

. Epistasis is when the expression of one gene is modified by the expression of one or more genes

. Chromosomal theory of inheritance is based on the fact that similar chromosomes paired in meiosis

. The eye color gene resides on the female X chromosome as determined by Morgan in flies

. Traits are determined by sex genes are sex-linked. Sex in fruit flies is based on # of X chromosomes

. In fruit flies Y chromosome is shorter, and 2X chromosomes = female, 1X and 1Y chromosome = male

. Sex chromosomes are dissimilar but still they pair during meiosis and mitosis

. Cross of female red eye fly (2X) with white eye male (xy) gives all red eye F1 progeny

. F1 female (Xy) crossed with F1 male (Xy) gives F2 as 2 female red eye and 2 male white eyes

.  Testcross F1 female (Xy) with male (xy) gives male and female red eye + male and female white eye

. Testcross indicates that white -eyed females are viable and that X chromosome is linked to eye color

. Sex determination varies across organisms. In humans 2X = female, XY = male

. Male birds have 2Z and female ZW. Some insects are either XX female or XO male (where O means zero)

. Honeybees are diploid females and haploid male

. Humans have 22 autosomes + X + Y (highly condensed). Default for humans is female

. In organisms with XY, few Y are expressed, thus a single recessive can produce recessive phenotype

. As a result, certain diseases affect more males, such as color blindness and hemophilia

.  Dosage compensation ensures equal expression of genes from sex chromosomes despite different #s

.  In female somatic cells 1X is randomly inactivated and highly condensed into a Barr body.

. Female heterozygous for genes on X are genetic mosaic such as the Calico cat

. Traits controlled by genes of mitochondria and chloroplasts don’t follow chromosome theory

 . Genes from mitochondria are often passed by one parent, usually the mother = maternal inheritance

. In genomic imprinting, the phenotype from a mutant allele depends on which parent contributed:

. Partial deletion on chromosome 15 in mother causes Angelman syndrome, but Prader-Willi in father

. igf2 (mice) encodes critical growth factor. Phenotypes depend on who gives the mutant allele

. Epigenetics is a mitotically and/or meiotically change in gene function without change in DNA sequence

. Epigenetics involves DNA methylation, non-coding RNAs, nuclear organization, protein alteration

. Genetic mapping using gene location are helpful to determine crossover to get recombinant gametes

. Crossing over exchanges alleles and the Creighton-McClintock experiment using maize proved it:

. Physical genetic material exchange occurs in genetic recombination and is the basis for genetic maps

.  As distance on a chromosome increases, so does the probability of crossover between gene loci

. Distance between genes is proportional to the frequency of recombinant events

. Recombination frequency = recombinant progeny/ total progeny. 1 mu = 1 cM = 1% recombination

.  Recombination is the basis for genetic maps using two-point cross or multiple crossovers

. If homologues undergo 2 crossovers between loci, the parental combination is restored

. Odd #s of crossovers gives recombinant gametes; 0 or even #s produces parental gametes

. Relationship between true distance on a chromosome and recombination frequency is not linear

. 3-point testcross allows tracking recombination events on either side of middle gene

. 3-point crosses are good to see the order of genes and 2-point crosses are good to see distances

. Some human traits are controlled by one gene and some exhibit dominant and recessive inheritance

. Dominant pedigree is juvenile glaucoma appearing in every generation

.  Recessive pedigree is albinism due a nonfunctional allele for enzyme tyrosinase. Parents are unaffected

. Hemophilia: sex-linked disorder caused by X-linked recessive allele. Females are asymptomatic carriers

. Sickle cell anemia, caused by one amino acid change in hemoglobin leads to impaired oxygen delivery

. Sickle cell allele prevalent in Africa reduces life span but gives resistance to malaria

. Cystic fibrosis (mucus clogging lungs, liver and pancreas) is a failure in Cl ion transport and is recessive

. Phenylketonuria (brain developing failure) is recessive, caused by a defect in phenylalanine hydroxylase

. Huntington disease (deterioration of brain tissue) is dominant due a defect in an inhibitor in brain cells

. Tay-Sachs disease (child CNS deterioration) is recessive due to defective lysosomal HEX A, a lipid breaker

. Hypercholesterolemia is dominant and due to abnormal cholesterol cell surface receptors

. Muscular dystrophy is X-linked recessive due to degradation of myelin of muscle-stimulating nerves

. Nondisjunction is failure of homologues or sister chromatids to separate during meiosis

. Aneuploidy (lethal) is gain (Trisomy) or loss (Monosomy) of a chromosome as a result of nondisjunction

. Human embryos trisomic for autosomes 13, 15, 18 die w/in months; 21 & 22 survive to adulthood

. Down syndrome, trisomy 21 may be a full or part translocation and it’s influenced by mother’s age

. Nondisjunction of sex chromosomes are not severe but causes some abnormal features

. Sex nondisjunction syndromes: females XXX, XO (Turner); males XXY (Klinefelter), XYY (Jacob)

. Early gene detection uses amniocentesis (fluid) or chorionic villi sampling (CVS, placental cells)

. Molecular markers use short (2-4 bases) tandem repeats (STR) that can differ in repeat number

. Single-nucleotide polymorphisms (SNPs) affect a single base and are used in forensic analysis

. Genetic maps are made with genetic markers from related individuals uses large amounts of data

. Association studies include phenotype ç=>  genotype are used to discover underlying genes in populations using electronic health records, show high levels of pleiotropy.