TS

Cell Cycle, Checkpoints, Cancer, Meiosis, and Sex Determination (Vocabulary)

G1 Checkpoint (Restriction Point)

  • Purpose: determine if all conditions are favorable for cell division to proceed

  • Also called the restriction point; cells irreversibly commit to division if passed

  • Checks include:

    • Adequate cellular reserves

    • Adequate cell size

    • DNA damage assessment (DNA damage if present should prevent progression)

  • Outcome: if requirements are not met, cells do not enter S phase

G2 Checkpoint

  • Location: end of G2 phase

  • Purpose: prevent entry into mitosis if conditions aren’t met

  • Checks include:

    • Cell size adequacy

    • Protein reserves sufficient for mitosis

    • Most importantly, ensure chromosomes have been fully replicated and are not damaged

  • If replication is incomplete or DNA is damaged, entry into mitosis is blocked

M Checkpoint (Spindle Checkpoint)

  • Location: end of mitosis, before cytokinesis

  • Also called the spindle checkpoint

  • Purpose: ensure all sister chromatids are correctly attached to spindle microtubules from opposite poles

  • Mechanism: kinetochores must be firmly anchored to spindle fibers before anaphase proceeds

  • Rationale: separation of sister chromatids in anaphase is irreversible; cycle cannot proceed until proper attachment is confirmed

  • Outcome: progression to cytokinesis only if all chromatids are correctly attached

Cancer, Genomic Alterations, and p53

  • Cancer cells: often no longer respond to normal growth and death signals; originate within tissues and become progressively abnormal as mutations accumulate

  • Common feature: unchecked proliferation beyond normal tissue boundaries

  • Cancer mutation burden: according to the Cancer Genome Project, most cancer cells possess 60 or more mutations

  • HeLa cells (Henrietta Lacks): famous cancer cell line still used in research; ethical discussions around derivation and usage of patient-derived cells

  • p53 tumor suppressor protein:

    • Induced by cellular stress signals (e.g., oncogene activation, DNA damage, hypoxia)

    • Can follow two pathways: 1) Cell cycle arrest with DNA repair

      • Arrests cycle (often via G0/G1) and activates DNA repair enzymes

      • DNA repair enzymes example: polymerases such as ext{DNA polymerase } \lambda and ext{DNA polymerase } \mu

      • After repair, cell cycle restarts
        2) Apoptosis (programmed cell death)

      • Characterized by cell shrinkage, membrane blebbing, organelle breakdown, nucleus collapse, and fragmentation

      • Fragmented cell parts are cleared by macrophages via phagocytosis

  • The dual role of p53 helps prevent propagation of damaged DNA and can trigger cell death when damage is irreparable

Basics of Sexual Reproduction in Eukaryotes; Genetics Primer

  • Reproduction and viability:

    • Viable offspring: capable of continuing parental genetic lineage

    • Offspring typically resemble parents but also differ due to genetic variation

  • Heredity vs Inheritance:

    • Heredity: transmission of genetic traits from parents to offspring

    • Inheritance: pathway and expression of genetic traits across generations

  • Genetics: scientific study of genes, genetic variation, and heredity in organisms

Eukaryotic Division: Mitosis vs Meiosis

  • Two main divisions:

    • Mitosis: somatic (body) cell division; produces somatic diploid cells that are genetically identical to the parent cell

    • Meiosis: division for germ (reproductive) cells; produces gametes with half the chromosome number (haploid) and generates genetic variation

  • Haploid vs Diploid:

    • Diploid (2n): two sets of chromosomes (one from each parent); in humans, 2n = 46; gametes are haploid with n = 23

    • Haploid (n): a single set of chromosomes; germ cells (gametes) are haploid

  • Chromosome counts:

    • Somatic cells: diploid, 2n = 46 in humans

    • Germ cells (gametes): haploid, n = 23 in humans

  • Sexual life cycles vary: some organisms are haploid-dominant, others diploid-dominant (humans are diploid-dominant)

Interphase and Meiosis vs Mitosis: Key Differences

  • Mitosis (somatic):

    • Interphase: DNA replication in S phase; each chromosome forms sister chromatids (two identical copies)

    • Prophase: chromosomes condense; mitotic spindle forms

    • Metaphase: chromosomes align on the metaphase plate

    • Anaphase: sister chromatids separate to opposite poles

    • Telophase & Cytokinesis: nuclear envelopes reform; cytoplasm divides; two diploid, genetically identical daughter cells produced

  • Meiosis (germ cells; two rounds of division with no DNA replication between them):

    • Meiosis I: reduces chromosome number by separating homologous chromosomes

    • Meiosis II: separation of sister chromatids, like mitosis, yielding four haploid gametes

    • Cytokinesis occurs after Telophase I and after Telophase II (resulting in four haploid cells)

  • Purpose differences:

    • Mitosis: growth, tissue repair, asexual reproduction; produces identical diploid cells

    • Meiosis: sexual reproduction; generates genetic diversity and haploid gametes

Interphase Details for Mitosis vs Meiosis

  • Mitosis interphase: each chromosome duplicates during S phase; produces two genetically identical sister chromatids

  • Meiosis interphase: chromosomes are duplicated, but they are not yet visible; DNA has been replicated; chromosomal visibility occurs later during meiosis I

Meiosis I: The First Division; Key Events

  • Prophase I:

    • Homologous chromosomes pair up and undergo synapsis, forming a tetrad (also called a bivalent)

    • Crossing over occurs: exchange of segments between non-sister chromatids within homologous chromosomes

    • Result: genetic recombination (variation) arises from physical exchange of DNA segments

    • Synaptonemal complex forms to stabilize pairing during crossing over; known as synapsis

    • Crossing over creates chiasmata; genetic material is exchanged between chromatids

  • Metaphase I:

    • Tetrads line up on the central plane (metaphase plate)

    • Random orientation (independent assortment) of homologous chromosome pairs occurs; each pair aligns independently of others

    • There is no single fixed order of alignment; alignment is random with respect to maternal/paternal origin

  • Anaphase I:

    • Homologous chromosomes separate and migrate to opposite poles

    • Sister chromatids remain held together at the centromere; reduction division occurs

  • Telophase I:

    • Each pole contains a haploid set of chromosomes (still composed of two sister chromatids per chromosome)

    • Cytokinesis typically follows, producing two haploid cells

Meiosis II: The Second Division

  • Prophase II:

    • Spindle apparatus forms in each haploid daughter cell

  • Metaphase II:

    • Chromosomes (each still consisting of two sister chromatids) align on the metaphase plate

    • Kinetochores attach to spindle fibers from opposite poles

  • Anaphase II:

    • Sister chromatids separate and move to opposite poles

  • Telophase II:

    • Nuclear envelopes re-form around the sets of chromosomes; cytokinesis divides each cell

  • End result: four haploid gametes; all unique

Unique Features and Sources of Genetic Variation in Meiosis

  • Crossing over (in Prophase I):

    • First major source of genetic variation

    • Occurs between homologous non-sister chromatids; creates new chromosomal combinations

  • Synapsis: formation of tetrads and stabilization of homologous pairing by the synaptonemal complex

  • Independent assortment (in Metaphase I):

    • Random orientation of chromosome pairs creates a large number of possible gamete combinations

    • Variation source two: number of possible alignments = 2^n, where n is the haploid number per set

  • Random fertilization (zygotic variability):

    • Any sperm can fertilize any egg; adds another layer of variability

  • Example: human human gamete combinations

    • n = 23; number of possible combinations per gamete: 2^{n} = 2^{23} = 8{,}388{,}608

    • If you consider two parents, total diploid combinations possible at fertilization: 2^{n} imes 2^{n} = 2^{46} = 70{,}368{,}744{,}177{,}664 ext{ (approximately } 7.04 imes 10^{13} ext{)}

    • Some sources round to about 64 trillion; the exact calculation is $$2^{46} ext{ (about } 7.04 imes 10^{13} ext{)}

  • Significance of genetic variation:

    • Environmental adaptation: variants help tolerate changing environments

    • Disease resistance: some individuals have resistance against diseases/parasites

    • Reproductive success: diversity reduces risk of shared deleterious traits

    • Innovation: emergence of new traits improves population adaptability and ecosystem function

    • Inbreeding depression: reduced genetic diversity can lower fertility and resilience to disease

    • Ecosystem implications: diverse populations perform various ecological roles (nutrient cycling, pollination, predator-prey dynamics)

Reduction of Chromosome Number and Gamete Formation (Meiosis) – Practical Summary

  • End products of meiosis: four haploid gametes; each has half the chromosome number of the parent (n)

  • Reduction division: meiosis I reduces chromosome number by separating homologs; meiosis II separates sister chromatids

  • Reduction and recombination ensure genetic diversity in offspring

  • The concept of independent assortment and crossing over contributes to diversity across generations

Chromosome Numbers and Gametogenesis: Quick Reference

  • Humans:

    • Somatic cells: 2n = 46 (diploid)

    • Gametes: n = 23 (haploid)

    • Zygote after fertilization: 2n = 46 (diploid)

  • General rules:

    • Diploid number is often denoted as 2n; haploid number as n

    • Meiosis yields haploid gametes; fertilization restores diploidy

Sex Determination: SRY Gene and Beyond

  • SRY gene (Sex Determining Region Y) protein:

    • Located on the Y chromosome

    • Expressed in a specific embryonic window to regulate differentiation toward testes

    • Binds DNA and bends it to regulate the SOX9 gene, a critical step in differentiating precursor cells into Sertoli cells

    • Leads to the formation of testes when functional

    • Absence of functional SRY leads to development of female structures

  • Experimental evidence:

    • Knockout or suppression of SRY can lead to female development despite XY genotype (e.g., in rabbits/mice)

    • Insertion of SRY or its functional analog can induce testis development in some contexts

  • Sex determination systems (diverse across taxa):

    • Genetic sex determination (GSD):

    • Mammals and birds typically use chromosomal systems

    • Humans: male XY (male heterogamety); females XX

    • Birds: female heterogamety; females ZW, males ZZ

    • Temperature-dependent sex determination: some reptiles and fish rely on incubation temperature

    • Other systems mentioned: XO sex determination; haplodiploidy (common in some insects)

  • Common terms:

    • Male heterogamety: males produce two different sex chromosomes (e.g., XY in humans)

    • Female heterogamety: females produce two different sex chromosomes (e.g., ZW in birds)

  • Notable example referenced: clownfish — intriguing cases of sex determination and sex change in some species (to be explored in zoology)

Terminology Recap and Conceptual Links

  • Kinds of life cycles:

    • Diploid-dominant life cycle (humans): most of life is diploid; meiosis and fertilization produce haploid gametes and restore diploidy

    • Haploid-dominant life cycle (some algae/fungi): most of life is haploid; meiosis still occurs to produce spores/gametes for reproduction

  • Key terms:

    • Zygote: diploid cell formed by fertilization of two gametes

    • Synapsis: pairing of homologous chromosomes during Prophase I

    • Synaptonemal complex: protein structure that stabilizes synapsis and supports crossing over

    • Tetrad (bivalent): paired homologous chromosomes forms a four-chromatid structure during Prophase I

    • Chiasmata: visible crossover points where chromatids exchange material

    • Independent assortment: random orientation of homologous pairs during Metaphase I

    • Recombination: exchange of genetic material during crossing over, generating new allelic combinations

    • Phagocytosis: macrophages clearing cellular debris after apoptosis

Practical and Ethical Notes

  • HeLa cells: widely used in cancer research; originate from Henrietta Lacks; highlight ethical considerations in using patient-derived cells without consent

  • SRY-related experiments illustrate how genetic determinants can drive sexual development; nuance in species differences and manipulation implications

  • The variety of sex determination mechanisms across taxa shows the diversity of evolution in reproductive strategies

Study Tips and Key Takeaways

  • Remember the three sources of genetic variation in meiosis: crossing over (Prophase I), independent assortment (Metaphase I), and random fertilization

  • Distinguish mitosis vs meiosis by end products and chromosome number: mitosis yields two diploid, identical daughter cells; meiosis yields four haploid, genetically diverse gametes

  • Be able to identify where in meiosis each event occurs: crossing over in Prophase I; independent assortment in Metaphase I; sister chromatid separation in Anaphase II

  • Know the checkpoint order and purposes: G1 (restriction point) -> G2 -> M (spindle) checkpoints regulate progression through the cell cycle

  • Understand SRY’s role in sex determination and how genetic vs environmental factors can influence sex determination in different species

  • Connect these concepts to real-world biology: cancer biology (p53 pathways), reproductive biology (gametogenesis), and evolutionary genetics (variation and adaptation)