Lecture 3 - Cell Cycle Mitosis and Meiosis

Binary fission

Type of cell division by which prokaryotes (bacteria and archaea) reproduce; a form of asexual reproduction

Process of binary fission

Chromosome replicates starting at the origin of replication → the two copies of the origin move toward opposite ends as the cell elongates → a division septum forms → the cell separates into two daughter cells

Meiosis (life cycle definition)

Process where a diploid cell gives rise to haploid cells (gametes)

• sexual life cycle

Fertilization

Process where two haploid cells (gametes) fuse to form a diploid zygote

• restoring the diploid state; gametes usually come from different individuals

Three main categories of sexual life cycles

1) Diploid-dominant

2) Haploid-dominant

3) Alternation of generations

Diploid-dominant life cycle

• The multicellular diploid stage is the most obvious life stage

• the only haploid cells are the gametes; found in humans and most animals

Haploid-dominant life cycle

• The multicellular (or sometimes unicellular) haploid stage is the most obvious life stage;

• the single-celled zygote is the only diploid cell; found in fungi and some algae

Alternation of generations

• Both the haploid and diploid stages are multicellular (dominant to different degrees in different species)

• found in plants and some algae

Gamete

• A reproductive cell of an animal or plant (e.g., sperm or egg);

• haploid

Germ cells

• Special diploid cells made in the gonads early in animal embryo development;

• they divide by mitosis to make more germ cells, and some undergo meiosis to make haploid gametes

Gonads

Organs that produce gametes: testes and ovaries

Zygote

A diploid cell resulting from the fusion of two haploid gametes; a fertilized ovum

Human sex cells

• Egg and sperm cells

• contain a single set of chromosomes and are haploid

Organisms with a haploid-dominant life cycle

• Most fungi and some protists (unicellular eukaryotes)

• the "body" (mature, ecologically important form) is haploid

• Ex: Black bread mold

Hyphae

• Multicellular, thread-like haploid structures of fungi

• in bread mold sexual reproduction, hyphae from two compatible individuals (+ and − mating types) grow toward each other

Zygosporangium

• Structure formed where two compatible hyphae meet;

• contains multiple haploid nuclei from the two parents

Zygospore

• Diploid structure formed after nuclear fusion

• can stay dormant for long periods, then under the right conditions its diploid nuclei undergo meiosis to make haploid spores

Spores (bread mold)

• Single cells containing haploid nuclei released after meiosis of the zygospore

• they grow by mitosis into new hyphae

Phases in alternation of generations

A haploid sexual phase (gametophyte) and a diploid asexual phase (sporophyte)

Gametophyte

• The haploid multicellular plant (or alga)

• makes gametes using specialized cells

Why is meiosis not directly involved in making gametes in gametophytes?

Because the gametophyte is already haploid, so it makes gametes by mitosis

Sporophyte

• Diploid multicellular plant formed from the zygote by many rounds of mitosis

• specialized cells undergo meiosis to produce haploid spores

Alternation of generations cycle order

Haploid gametes fertilize → diploid zygote → mitosis → sporophyte → meiosis (in sporangia) → haploid spores → germination/mitosis → gametophyte → makes egg and sperm

Sporophyte vs gametophyte in seed plants

• In seed plants (e.g., magnolia trees, daisies), the sporophyte is much larger

• what we consider the "plant" is almost entirely sporophyte tissue

Cell cycle

Four-stage process:

cell increases in size (G1), copies its DNA (S), prepares to divide (G2), and divides (M)

Interphase

The part of the cell cycle made of G1, S, and G2 (everything except M phase)

G1 phase

• Gap 1: cell grows

• metabolic changes prepare the cell for division

• cellular contents (excluding chromosomes) are duplicated

• many cells check that nutrient levels are high enough to complete division

Restriction point

Point in G1 after which the cell is committed to division and moves into S phase

S phase

• Synthesis phase: chromosomes are duplicated (all 46 in humans)

• each chromosome now consists of two sister chromatids

G2 phase

• Gap 2: metabolic changes assemble cytoplasmic materials needed for mitosis and cytokinesis

• the cell "double checks" duplicated chromosomes for errors and makes repairs

M phase

Nuclear division (mitosis or meiosis) followed by cytoplasmic division (cytokinesis)

G0

• Cell cycle arrest

• a resting state where the cell exits the cycle

Order of mitosis stages

Prophase → Prometaphase → Metaphase → Anaphase → Telophase (then Cytokinesis)

Prophase (mitosis)

• Chromosomes condense and become visible

• spindle fibers emerge from the centrosomes

• nuclear envelope breaks down

• centrosomes move toward opposite poles

Prometaphase

• Chromosomes continue to condense

• kinetochores appear at the centromeres

• mitotic spindle microtubules attach to kinetochores

Metaphase (mitosis)

• Chromosomes line up at the metaphase plate

• each sister chromatid is attached to a spindle fiber from opposite poles

Anaphase (mitosis)

• Centromeres split in two

• sister chromatids (now called chromosomes) are pulled toward opposite poles

• certain spindle fibers elongate the cell

Telophase (mitosis)

• Chromosomes arrive at opposite poles and decondense

• nuclear envelope reforms around each set

• mitotic spindle breaks down

• spindle fibers keep pushing poles apart

Cytokinesis in animal cells

A cleavage furrow separates the daughter cells

Cytokinesis in plant cells

A cell plate (precursor to a new cell wall) separates the daughter cells

Three components required for eukaryotic chromosome maintenance during cell division

Centromeres, telomeres, and origins of replication

Centromere (definition)

• Specialized DNA sequence of a chromosome that links a pair of sister chromatids (a dyad)

• spindle fibers attach to it via the kinetochore during mitosis

Kinetochore

Complex of proteins associated with the centromere during cell division, to which spindle microtubules attach (has inner and outer kinetochore)

Two major chromosomal events of S phase

1) DNA replication copies each chromosome completely

2) sister chromatid cohesion is established by ring-shaped cohesin molecules

Cohesin

Ring-shaped protein hypothesized to encircle the two copies of replicated DNA, holding sister chromatids together (sister chromatid cohesion)

Chromatid

• Each copy of a duplicated chromosome

• the two chromatids of a pair are sister chromatids

Three major events of M phase (mitosis)

1) The two kinetochores of each sister chromatid pair attach to opposite spindle poles

2) cohesion is eliminated by destroying the cohesin ring

3) sister chromatids are segregated to opposite poles

How many centromeres does a normal chromosome have?

One

What happens to centromeres after chromosome replication?

• Each copy of the centromere directs formation of a kinetochore

• the two kinetochores bind opposite spindle poles and are pulled to opposite sides of the cell

Chromosome with no centromere

Cannot attach to the spindle, so it is randomly distributed to daughter cells (one daughter may get two copies and the other none)

Chromosome with two or more centromeres

Frequently broken during segregation

Centromere size in different organisms

Varies dramatically:

S. cerevisiae ~125 bp (CDE I-III)

S. pombe 40-100 kb

D. melanogaster ~400 kb

human 240 kb to several Mb

Meiosis (overview)

• Sex cell division: one germ cell → four gametes

• two divisions, each with prophase, metaphase, anaphase, telophase

What precedes meiosis?

Interphase, in which DNA is replicated so chromosomes consist of two sister chromatids

Interkinesis

Optional growth phase between meiosis I and meiosis II; NO DNA replication occurs

Final outcome of meiosis

Four haploid daughter cells, which may all be genetically distinct if crossing over occurs in prophase I

What separates in meiosis I?

Homologous chromosomes

What separates in meiosis II?

Sister chromatids

Reduction division

Meiosis I: diploid → haploid, in which homologous chromosomes are separated, reducing the chromosome number by half

Prophase I

Chromosomes condense, nuclear membrane dissolves, homologous chromosomes pair to form bivalents (synapsis), and crossing over (recombination) occurs

Bivalent (tetrad)

• A pair of synapsed homologous chromosomes

• contains a total of 4 chromatids

Metaphase I

Spindle fibers from opposing centrosomes connect to bivalents (at centromeres) and align them along the middle of the cell

Anaphase I

• Spindle fibers contract and split the bivalent

• homologous chromosomes move to opposite poles

• independent assortment occurs

Telophase I

Chromosomes decondense, nuclear membrane may reform, cell divides (cytokinesis) to form two haploid daughter cells

Linkage

Co-inheritance of two genes (loci) on the same chromosome

How does distance affect linkage?

The closer two genes are, the more likely they show linkage, because crossovers occur by chance and more DNA between genes means a greater chance of a crossover

Linkage group

Group of genes mapped (using crossovers) to show their relative order on a chromosome or part of a chromosome

Map unit (mu)

• Unit of distance between genes, based on recombination frequency

• 1 mu = 1% recombination between 2 genes

Parental vs recombinant chromosomes

• Parental: allele combinations same as the parents (e.g., AB, ab) from meioses with no crossover between genes

• Recombinant: new combinations (e.g., Ab, aB) from a crossover between the genes

Why does recombination frequency reflect gene distance?

Crossovers in meiosis I happen at random positions, so a short distance is a small "target" for crossovers (few events) while far-apart genes recombine more often

Use of recombination frequency

Estimating the relative distance between two genes on a chromosome (their degree of linkage)

How do you know two genes are linked in a test cross?

• The four classes of offspring are not produced in equal numbers

• parental types are over-represented and recombinant types are under-represented

Recombination frequency (RF) formula

RF = (Recombinant offspring ÷ Total offspring) × 100%

Meiosis II (overview)

• Second division

• separates sister chromatids (which may not be identical due to crossing over in prophase I), producing four haploid gametes

Prophase II

Chromosomes condense, nuclear membrane dissolves, centrosomes move to opposite poles (perpendicular to before)

Metaphase II

Spindle fibers from opposing centrosomes attach to chromosomes at the centromere and align them along the cell equator

Anaphase II

Spindle fibers contract and separate sister chromatids; chromatids (now called chromosomes) move to opposite poles

Telophase II

Chromosomes decondense, nuclear membrane reforms, cells divide (cytokinesis) to form four haploid daughter cells

Chromosome behavior in meiosis

• Two rounds of chromosome segregation follow a single replication

• sister chromatids are held together by cohesion

How many crossovers per pair of homologues?

At least one crossover (CO) per pair of homologues is always observed

What forms the bivalent at metaphase I?

Crossovers + sister chromatid cohesion physically link the recombined homologous chromosomes

Cohesion at anaphase I

• Released everywhere except at the centromeres

• homologs segregate while sister chromatids stay together

Cohesion at metaphase II / anaphase II

Centromeric cohesion is destroyed, allowing sister chromatids to segregate to opposite poles starting at anaphase II

Mitosis: duplications and divisions

Chromosomes duplicate once; cell divides once

Meiosis: duplications and divisions

Chromosomes duplicate once; cell divides twice

Outcome of mitosis

Two diploid daughter cells that are genetically identical

Outcome of meiosis

• Four haploid daughter cells that are NOT genetically identical

• they contain different combinations of homologues due to crossover

DNA synthesis: mitosis vs meiosis

Occurs in S phase of interphase in both

Synapsis and crossover: mitosis vs meiosis

Meiosis: during prophase I; Mitosis: do not occur

Lining up at the metaphase plate: mitosis vs meiosis

• Homologous pairs: metaphase I only (not in mitosis)

• sister chromatids: metaphase II in meiosis and metaphase in mitosis

Trait

A specific characteristic of an individual; determined by both genes and environment

Genotype

The genetic composition of a trait

Phenotype

The visible or otherwise observable, measurable trait produced by a genotype

Homozygous

Genotype with two identical alleles in a gene pair

Heterozygous

Genotype with two different alleles in a gene pair

Dominant allele

Allele whose trait appears in both homozygous and heterozygous individuals

Recessive allele

Allele whose trait appears only in homozygous individuals

Codominant allele

Allele whose trait reflects the combination of two different alleles (both show)