October 7th, 2013 Biology 2C03: Genetics

What is a Chromosome?

Chromosomal Theory of Inheritance - A collection of studies revealed that genes are on chromosomes. In fact,

multiple genes are present on each chromosome

What is a Chromosome? How many do we have?

- Haploid: one copy of genetic material subdivided into chromosomes Can still replicate and form sister chromatids Single copy

- Diploid: two copies of genetic material subdivided into chromosomes Same genes but may have different alleles

- Ploidy: the number of complete chromosome sets - Homologous chromosomes: a pair of matching chromosomes, one homolog

from each parent - Most eukaryotes: diploid adults, haploid gametes (sperm/ovum) - Why diploid?

Diploid or polyploidy have genetic buffering - What about haploid and polyploidy? - Many plants are polyploidy - Some animals (e.g., certain fishes and amphibians) are also polyploid

Chromosome Structure

- Single chromosome with two sister chromatids - Two copies of chromosomes: undergo duplication in S phase so each

chromosome have two sister chromosomes - Telomeres: structures at the top

- Centromere: holding sister chromsomes together - Kinetochore: wehre spindle microtubules attach - Centromere is not defined as the middle of chromsomes as they may exist on

all parts of the chromosome Metacentric: located at the center Submetacentric: slightly off centered (chromosomes 1 and 3) Acrocentric: far on the edge, peaks at the top but not completely (13,

14, 15, 21, 22) Telocentric: no telocentric chromosomes in humans; centromere

located at the end - Eukaryotic chromosomes exist in four major types based on the position of

the centromere

Human Karyotype

- Karyotype: G-banding Dark regions are heterochromatic Light regions are euchromatic, early replicating

- Karyotype: painting probes - Human chromosome set: 23 chromosomes. Here we see two copies of the set

(diploid)

Autosomes and Sex-Chromosomes

- Chromosomes can be distinguished as: Autosomes: present in the same copy number in both males and

females; number and morphology of autosomes is species-specific Sex-chromosomes: present in different copies in males versus

females; single pair of sex chromosomes or a single sex chromosome (XX female; XY male)

Questions we need to Answer

- How do we know that genes are on chromosomes? - What is the structure of a chromosome? - How does the structure of a chromosome affect gene expression?

Chromosomal Basis of Heredity

- Walter Flemming, 1882 First to detail the process of chromosomal movement during mitosis Identified steps of mitosis from the condensation of chromosomes

into coiled ‘threads’ (prophase) thorugh the separation of these threads into two ‘skeins of yarns’, when the scaffold of the nucleus reappears

Termed process Karyomitosis (‘threadlike metamorphosis of the nucleus’)

The Chromosome Theory of Inheritance

- The union of cytology and genetics - Cytology: the study of cell structure (chromosomes) - Genetics: the study of heritable factors (genes) - 1902: Walter Sutton and Theodor Boveri developed the chromosome theory

of inheritance

- Genes are located on chromosomes (chromosomes and genes show similar patterns of inheritance)

- What is the accumulated proof for this theory? Evidence for the Chromosome Theory of Inheritance

- Much evidence that suggested that heritable information is found on chromosomes: 1) Chromosome number is species specific 2) Blakeslee: Jimsonweed (Datura), plants with different chromosome sets

display different phenotypes Induced aneuploidy Mutants were trisomy for different chromosomes Associated phenotype with number of chromosome present

3) Eleanor Carothers: meiosis in grasshoppers, first cytological evidence for independent assortment chromosomes

4) Sex chromosomes: chromosomes represented differently in the two sexes 5) Patterns of chromosome movements parallel Mendel’s patterns of

inheritance What is the Function of Mitosis?

- Replication of identical cells – one cell produces two cells that are genetically identical to one another and to the original mother cell

- One diploid cell (2n) = two diploid cells (2 x 2n) - Where and when does mitosis occur: all cells of the body (except for

gametes) reproduce and multiply by mitosis - What happens if chromosomes fail to separate: this is called nondisjunction,

extra copies Stages of Mitosis

- Interphase: nuclear membrane present and chromosomes are relaxed - Prophase: chromosomes condense, each contain 2 chromatics and mitotic

spindle forms, homologous chromosomes - Prometaphase: nuclear membrane degrades, microtubules attach to sister

chromatids - Metaphase: align - Anaphase: sister chromatids are being pulled to opposite poles - Telophase: nuclear membrane reforms, chromosomes relax

Mitosis Movies

- Animations of mitosis in a cell with one pair of chromosomes - Time-lapse sequence of a purple urchin embryo in which all of the cells in the

28-cell embryo undergo mitosis nearly synchronously What is the Function of Meiosis?

- Germ line cells undergo meiosis in order to produce haploid gametes - What meiosis-specific events are required?

Meiosis

- Meiosis: can be divided into two stages = two distinct cell divisions - There are meiosis-specific events that help to explain many observations in

genetics, including: Mendel’s first law: principle of equal segregation

Mendel’s second law: principle of independent assortment Genetic recombination

Meiosis I: First Division

- Start with 2n cell - Late prophase I: Pairs of homologous chromosomes come together - Prophase I in meiosis is the longest stage: crossing over and genetic

recombination - Metaphase I: homologous chromosomes align on metaphase plate and

separate during anaphase I - Anaphase I is a reductional division: (diploid to haploid) - Homologues separate and therefore alleles separate - Mendel’s first law: principle of equal segregation - Chiasmata in late prophase: meiosis specific event

Meiosis II: Second Division

- Sister chromatids separate during anaphase II - Anaphase II: an equational division - Now, replicated, paired sister chromatids separate - Products are haploid

Prophase I: Pairing of Homologues is a Meiosis-Specific Event

- Pair of homologous chromosomes were crossing over occurs in a bivalent - Ensures that each cell is getting one copy of the chromosome - Diplotene: chiasmata become visible - Non-sister chromatids in a bivalent that undergo breakage and reunion =

crossing over - The site of a cross over = chiasma (plural is chiasmata) - This physical event turns out to be very important in genetics as we will see

later

Metaphase/Anaphase I Transition

- It is this separation of homologues that explains Mendel’s first principle - Genetic recombination: different combinations of allele flip between the

homologous chromosomes - Meiosis specific events:

Metaphase: paired centromeres of homologues assemble on spindle Anaphase: paired centromeres separate and homologues are pulled to

opposite poles But, sister chromatids within a chromosome remain together

Mendel’s Second Law: Principle of Independent Assortment

- Each allele is separated independently - This is anaphase I - Pairs of homologues (tetrads) align on metaphase I spindle - The orientation of a each tetrad occurs independently - Either orientation is equally likely

Completion of Meiosis I

- Two cells, each is haploid with a mixed parental set of dyads

- Dyad: half a tetrad = paired sister chromatids joined at the centromere but no matching homologous chromosome

Metaphase/Anaphase II Transition

- Metaphase II: dyads assemble on spindle - Anaphase II:

Centromeres of paired sister chromatids separate This allows sister chromatids to segregate to opposite poles (compare

with anaphase of mitosis) Haploid cells (different from mitosis)

- Telophase II: 4 haploid cells (4 x n)

Meiosis Animations - One pair of chromosoems: 2n = 2 - Result: 4 haploid cells with n = 1

Mendel’s Principles and Meiosis

- This similarity in the pattern of chromosome inheritance and genetics inheritance is really a correlation

- We need proof that a gene resides on specific chromosomes - Metaphase I: principle of independent assortment - Anaphase I: principle of equal segregation