Mitosis and Meiosis

Cellular Reproduction - Mitosis and Meiosis

• Germ-line cells undergo meiosis, while somatic cells undergo mitosis.
• Humans have 23 chromosomes.
• Homologous chromosomes are a set of one maternal and one paternal chromosome that pair up during fertilization.
  • They have the same genes in the same loci, enabling alignment before separating during meiosis.
• Four types of chromosomes exist:
  • Metacentric: Centromere in the middle with long telomeres.
  • Submetacentric: Centromere skewed, making one arm shorter.
  • Acrocentric: One arm is very short.
  • Telocentric: Only one arm (e.g., Y chromosome).
• Interphase includes 3 steps:
  • G₁-phase: Cell gets bigger and copies organelles after division, but does not copy DNA.
    • A checkpoint near the end determines if cells should divide.
  • S-phase: DNA synthesis of a complete copy and a centrosome copy for sister chromatid creation and separation.
  • G₂-phase: Checks for DNA damage after replication, with cell growth and content reorganization for mitosis.
  • Autonomously replicating sequences (ARSs) enable DNA replication, originating in yeast chromosomes.
• Cell cycle checkpoints: Prolonged waits at checkpoints leads to cell death.
  • G₁ checkpoint: Determines if the cell should divide based on DNA duplication capacity.
    • Considers size, nutrients, molecular signals (growth factors), and DNA damage.
    • Cells commit to division after this checkpoint with no return.
    • If a cell receives no signal for DNA synthesis, it goes to G₀.
  • G2 checkpoint: Verifies if a cell can divide.
    • Checks for DNA damage and replication completeness from S-phase.
    • Cell death occurs if DNA cannot be repaired or replication is incomplete.
  • M-phase: Spindle checkpoint ensures even sister chromatid splitting to daughter cells.
    • It checks the binding of spindle fibers to kinetochores.
    • Gene expression almost completely shuts down.

Mitosis

• Mitosis consists of mitosis and cytokinesis.
  • Mitosis condenses DNA into chromosomes, pulled apart by mitotic spindles made of microtubules.
  • Cytokinesis splits the cytoplasm into two cells. Animal cells: Use a contractile ring (cytoskeletal fibers) to pinch inwards, forming a cleavage furrow. Plant cells: Build a cell plate (plasma membrane and cell wall components) in the middle to split into two.
• Go phase: The cell rests performing its job.
• Before mitosis (end of G₂): Chromosomes in the nucleus have two connected copies (sister chromatids) alongside a MTOC copy.
  • Topoisomerase 2 separates daughter chromatids during mitosis.
• Phases of mitosis:
  • Prophase: Involves preparing for division by breaking/building structures.
    • Chromosomes start to condense.
    • The mitotic spindle forms between two MTOCs that migrate to opposite cell ends. The nucleolus disappears.
  • Prometaphase: Chromosomes become very compact after condensing. The nuclear membrane breaks down, releasing chromosomes. Some microtubules form fibers that bind to chromosomes at their kinetochores (specialized histones at the centromere, the tightest connection point due to repetitive DNA). Microtubules not binding to kinetochores stabilize spindles by binding to opposite sides. Aster is a Microtubule cluster that corrects mitotic spindle positioning and orientation
  • Metaphase: Captured chromosomes are lined up in the middle. Chromosomes align along the "metaphase plate." Both kinetochores of each chromosome attach to microtubules extending from each spindle. Microtubules polymerize/depolymerize until binding to what they should connect. The spindle checkpoint ensures even sister chromatid splitting when separating.
  • Anaphase: Sister chromatids separate and are pulled to opposite cell ends. Sister chromatids separate, becoming individual chromosomes. Microtubules lengthen, pushing against each other to make the cell longer.
  • Telophase: The cell re-establishes previous structures as cytokinesis occurs. Mitotic spindle degrades. Two new nuclei form, each with a nuclear membrane and nucleolus. Chromosomes decondense and relax in each nucleus.
  • Spindle Assembly Checkpoint: This occurs between the end of metaphase and beginning of anaphase. Cells sense opposing forces of microtubules to kinetochores via motor proteins. Motor proteins on the kinetochore move to the spindle poles’ minus end, held together by cohesin. Once all chromosomes align correctly, MAD/Bub complex becomes inactive and release CDC20. CDC20 binds APC/C (APC), a ubiquitin ligase that ubiquitinates Securin, to be recycled by the proteasome APC activation destroys M-cyclin, lowering M-CDK levels. Ubitquitination of securin releases Separase. Active Separase cleaves cohesin, the “glue” binding sister chromatids. Cohesin is placed during DNA replication in the S-phase
  • This allows motor proteins on kinetochores to move towards spindle poles.

Meiosis

• Meiosis produces haploid gametes from diploid germ-line cells. Starting Meiosis I with 2 big metacentric and 2 submetacentric chromosomes splitting so that each cell has 1 metacentric and 1 submetacentric chromosome Meiosis II has the homologous sister chromatids separate and so end up with 4 cells that have 1 piece of DNA (chromatid) from both types of chromosomes
• Meiosis I: Separation of homologous chromosomes. Prophase I Centrosomes form as chromosomes condense Homologous chromosomes pair (synapsis). Crossing over (@ chiasmata) occurs as nuclear envelope breaks Occurs late in prophase I This exchange of genes is unique to the progeny!!! Nobody else has that same kind of genetic variation Metaphase I Homologous pair line up along the “metaphase plate" Cohesin that keeps the homologous chromosomes together gets broken down here to lead into Anaphase I Cohesin bound homologous chromosomes together at chiasmata Anaphase I Homologous pairs separate and move towards opposite poles Cohesin in the centromere of the chromosomes are protected by a protein called shugoshin Telophase I Chromosomes arrive at spindle poles and cytokinesis occurs
• Meiosis II: Separation of sister chromatids. Prophase II Chromosomes recondense Metaphase II Chromosomes align one across the other along the “equatorial plate" Anaphase II Sister chromatids separate and move towards opposite poles Shogosin gets degraded at the end of metaphase II to allow cohesin to be degraded as well Telophase II Cytoplasm completely divides once chromosomes arrive at spindle poles
• Genetic variation is produced by the random distribution that occurs in the chiasmata AS WELL AS the random assortment of homologous chromosomes in Anaphase I Number of different combinations = 2ⁿ where n = number of homologous chromosomes entering meiosis

Mitosis vs Meisosis?

• Mitosis:
  • Produces 2 genetically identical daughter cells. Both daughter cells have 2 copies of each chromosome (meaning that the daughters are diploid)
• Meiosis:
  • Cross over means 4 genetically different daughter cells At the end of Anaphase I, the daughter cells are already haploid since the cells only have one of each chromosome... they just lose their sister chromatid of the same chromosome

Meiosis in Animals

• Spermatogenesis: Production of male gametes that occurs in the coiled seminiferous tubules of the testes.
  • Spermatogonium → Primary spermatocyte → Secondary spermatocytes (2) → Spermatids (4) which mature into sperm
• Oogenesis: Production of female gametes, commencing during uterus development- females have a set amount of primary oocytes.
  • Oogonium → Primary oocyte → Secondary oocyte (+ first polar body) → Ovum (+ second polar body)
• Sperm and ovum fusion (fertilization) to produce a diploid zygote.
  • Meiosis II in oogenesis can occur once sperm penetrates the secondary oocyte.

Heredity

• Key genetic terms:
  • Characteristic: Encoded by a gene.
  • Gene: Positioned on a chromosome at a locus.
  • Locus: Each homologue has a gene variant (allele).
  • Allele: Combined ways are represented by the genotype.
• Genotype: the appearance of characteristics, is the Phenotype. Heterozygotes → 2 alleles are different Homozygous → 2 alleles are the same
• Monohybrid Cross: This cross is between parents differing by one trait.
• Mendel's Pea Experiment results: The traits of the parent plant do not blend, which results in the phenotypes of a 3:1 ratio from the parents
• 4 key conclusions for heredity:

1. One character is encoded by two genetic factors.
2. 2 genetic factors (alleles) separate when gametes are formed.
3. Dominant vs Recessive alleles
4. 2 alleles separate with equal probability go to equal probability in the gametes.

• This was found by looking at the third generation of peas. Brought about the law of segregation

• Law of Segregation: During gamete production, the two hereditary factor copies segregate so that offspring acquire one factor from each parent.

  • The idea of "dominance" comes from the pea monohybrid cross-study.

• Chromosome theory of heredity: Mechanism explains Mendelian laws by linking chromosomes to Mendel's paired factors.

• Back cross and Punnett Square: Cross between F₁ and a parent to test the allelic dominance hypothesis.

• Test Cross: Cross between an individual with an unknown genotype and a homozygous recessive individual.

• Phenotypic Ratio:

  • 3:1 → parents = Aa x Aa → progeny = ¼ AA : ½ Aa : ¼ aa
  • 1:1 → parents = Aa x aa → progeny = ½ Aa : ½ aa

• Genotypic ratio:

  • 1:2:1 → parents = Aa x Aa → progeny = ¼ AA: ½ Aa : ¼ aa
  • 1:1 → parents = Aa x aa or AA x AA → progeny = ½ Aa : ½ aa or 1½ Aa : 1½ AA (respectively)

• Usually, genes derive their name from the phenotype they produce.

• Homozygous = same alleles.

• Heterozygous = different alleles.

• Dihybrid Crosses examine two traits at once, based on the “Independent Assortment” principle.

  • Alleles located on different chromosomes sort independently.
  • Discovered by Mendel's pea experiment

• Mendel's Principles:

  • First Law: Each individual possess 2 alleles encoding a trait → Before meiosis Alleles separate when gametes are formed → Anaphase 1 Alleles separate in equal proportions → Anaphase 1
  • Seconds Law: Alleles at different loci separate independently → Anaphase 1

• Probability is the likelihood of a particular event. Used in genetics to predict the outcome of a genetic cross

• Multiplication rule → Multiply for the probability of 2 independent events occurring at the same

  • For 2 independent events eventually occurring

• Addition rule → Add for the probability of 2 independent events eventually occurring. For 2 independent events eventually occurring

• Dihybrid crosses reveal the principle of independent assortment → apply probability and the

  • Branch diagram to dihybrid crosses

• Binomial Expansion → (p + q)^n where:

  • p = probability of an event
  • q = 1 - p
  • n = the number of times that event occurs

• Null hypothesis (H₀) is a "default" hypothesis. There is no relationship among experimental values.

• Alternative hypothesis (H₁)→ differences between observed and expected values cannot be explained by chance.

• In Mendelian crosses... H₀: Observed values = Expected values H₁: Observed values ≠ Expected values Alleles may not segregate and sort independently

• Degrees of freedom (dF) → Number of variables that can vary independently (# of

  • possible outcomes/phenotypes - 1)

• Chi-square test (x² test) → x² = ∑(O-E)²/Ε O = Observed E = Expected E = (row count x column count) / total number of observations

• Use Chi-square and dF on a table with p-values to determine null hypothesis validity p-value → Small p-value means that such an extreme observed outcome would be very unlikely under the null hypothesis If p > 5%, do not reject the null hypothesis, assume that there is no significant difference between the observed and expected values, and occurred by chance

• Note that you can only reject or fail to reject a null hypothesis. Hypothesis CANNOT BE ACCEPTED.*

• “A backcross" tests dominance by crossing a F1 individual with a genotype parent. Is a cross between an F1 individual and 1 parental genotype, and it tests the dominance of a trait. A testcross is a cross between an unknown genotype and a homozygous recessive genotype, which is used to find the genotype of the unknown Testcross →One parent shows the dominant phenotype for one or more genes and a second parent who is homozygous recessive for these genes

Sex Determination and Sex-Linked Traits

• Sexual Reproduction alternates between diploid and haploid Fertiliziation creates a diploid zygote, while meiosis produces haploid gametes

• Sex Determination Mechanisms: Diocious has either male or female structures, Monoecious has both structures only, but cannot produce both gametes

• Hermathrodites like flowers, have both sexes and therefore are able to produce both gametes. E.g. Pine trees with male and female cones

• Diecious: can be determined chromosomally, genetically and environmentally) Chromosomally: XX-XO system (males lack a Y chromosome) X + Y are only homologous at 2 pseudoautosomal chromosome regions Necessary for pairing XX-XY System (males have a Y chromosome) -- used in mammals XX - female XY - male Males are determined by presence of a single Y Chromosome Produces a 1.1 sex ratio from an X and Y crossing Males: Heterogametic sex Females: Homogametic sex ZZ-ZW System ZZ - male ZW - female

• Used for birds, snakes, butterflies, some amphibians, and fishes

• Haplodiploidy System Males- haploid Females- diploid

• Genetically only sex determining genes on undifferentiated chromosomes. Enviromentally: Limpet Example: Those limpetes are stacking on top of each other, and alternating the tower.

• Metamale: When a ration is X:A and less than 0.5 observed in fruit flies where A will be sets of autosomes.

• Metafemale: When ratio of the X:A is greater than 1 SRY gene is what provides the production of a protein to make the sex determining region Y protein in males.

Turner Syndrome: Humans with just just one X chromosome and usually are under delevoped, have sexual charatcersitics and are sterile.

"Anarogen receptos is defective in females. Cell insensitive to testostrone" Evolution Y-chromosome Mutation of a gene in one of the chromosomes caused “maleness” (so it evolved from an autosome) Mutations are other genes affected male characteristics Suppression from crossing over kept male traits with the male-determining gene Eventually, the lack of crossing over between X and Y led to how things are today X-linked recessive characteristics Color-blindness, so if a female is colorblind and homozygous, then her sons will definitely inherit the trait since they will only receive a Y chromosome from dad E.g. hemophilia being passed down British royalty because of incest Y-linked characteristics All males will exhibit the trait because they only receive a Y-chromosome from their dad Genetic Sex-Determining Systems: No sex chromosomes, only the sex determining genes Found in some plants, fungi, protozoans and fish Not based off a set/single chromosome

Environmental Sex Determination

• Limpets Position Stack Larva- settles on an unoccupied substrate develops into a female - produces chemicals To attract another larvae. The larvae - Atracted by the female settles on top of her Develope into males- become male - the orgianal males Eventuallt the males on top switch sex, developing to females
• Temperature in turtles

Overposition at beach and temperature helps determine sex Kobudia Fish: Based on size larger females (will switch to male.

• Reciprocal Cross- Hybridization involving pair of crosses + revese the sexes a associated with each genotype

• Nondisjunction → Occurs when the two X chromosomes fall to separate Calvin Bridges determined that the rare white-eyed males produced from the mating of true-breeding red-eyed females with white-eyed male Drosophila resulted from nondisjunction of X chromosomes in the female during meiosis

Nondisjuction in Melsols 1 = would produce XY gameters Melsols 2 would form either XX or YY gametes ( Normally would be either X or Y .)

• Dosage*
• **Compensation: Mechanisms THAT EQUALIZE THE AMOUNTS OF PROTEIN PRODUCED BYTHE SINGLE X AND BY two autosomes in the herogametic sex) .

Doubles the activity of the X gene to compensate for females.

• Happens because females have two females (XY) and so they should be more genes.
  • Since females more DNA and males → X chromsome is randamly deactivied The random and fired inactivation of excess genes that could lead leadin in the mossaism " Each barr body is the actual deactiviated body. " ( About that 15% % Of True Breeding: - kind of Breeding where parents would same of the phototype is homozygous for trait. "Extension to Mendelian Laws:

Key Terms

• Complete Damance: One alle is more cominant then then the other."

• Incomplete Dominance - Heterozygous phenotype its between given Hameypous phototybes -Codammance: *Bott alleles- Fully expressed

• Penetrance: (Indivaduls having a particular genotype expressing the phenotype.".

  • Variable penetrance, will have but not evary Indivil Expression: Degre
• • Penotybe: caused by some enviromental factor and is simdar to the the caused Mutatios. THE OF MAY AFFÉC DOMINANCE, Eig Organisms are functioning and defecy CrtR = make enough Crtr

• "In gene Interaction Genes Contribute to the Determination ofa Single Phenotypic Characteristic, while "* LEETAL ALLELE CAUSES DEATH PROGENY