updated 3/31/99

Lecture 17

Gametogenesis at the chromosomal level:
mitosis and meiosis

Reading

• None required
• Optional: Molecular Biology of The Cell. Second Edition. Chapter 15: Germ Cells and Fertilization, pp. 839-854. This is where most of the lecture material was summarized from but the majority of the material in this chapter is very complex. Graduate students should consider reading this.
• Diagrams from lecture

Lecture 17:

Definitions

• Chromosome - a linear DNA molecule
• Homologous chromosomes - chromosomes that have the same kind of genes in the same order
  • 1 copy from father, 1 copy from mother
  • humans have 46 chromosomes with 23 homologous pairs
  • also know as sister chromosomes
• Chromatid - after a chromosome has replicated in S phase, there are two chromatids. Each chromatid possess an identical sequence of DNA.
• Centromere - special region where spindle fibers attach

Grand Scheme

• Mitosis
  • 2N diploid cell
  • replicates
  • divides - two diploid daughter cells
• Meiosis
  • 2N diploid cell
  • replicates
  • division - two daughter cells, each 2N
  • division (without replication)- four daughter cells, each N (haploid)

Mitosis

• Cell Cycle - phases
  • Interphase
    • G0 - Gap 0 phase, a resting stage, low levels of MPF (Maturation Promoting Factor), 2N
    • G1 - Gap 1 phase, cell enters mitosis, low levels MPF, 2N
    • S - DNA synthesis occurs, low levels of MPF, 4N
    • G2 - Gap 2 phase, time before metaphase, MPF is low at the start and increases at the end of G2, 4N
  • M - M phase
    • Prophase - chromosomes condense, nuclear membrane disappears, MPF is increasing
    • Metaphase - chromosomes line up on spindle, MPF is at its peak level
    • Anaphase - chromosomes begin to pull apart, MPF declines to initiate anaphase
    • Telophase - spindles disappear, MPF is low, nuclear membranes begin to reappear
    • Cytokinesis - cell division, MPF low
• Sequence of Events
  • GO resting cell is triggered to enter cell cycle
  • progresses through G1, S, G2
  • enters M phase
    • short prophase
    • metaphase
      • nuclear membrane or envelope brakes-down
      • chromosomes attach to spindles via the centromeres
        • spindles are microtubules made of tubulin
      • homologous chromosomes align along side of each other
      • MPF activity is very high
    • anaphase
      • chromatids pull apart
      • MPF activity decreases
    • telophase
      • microtubules disappear
      • nuclear envelope reforms
    • cytokinesis
      • cell division

Meiosis

• Sequence of Events
  • Interphase - I
    • G0 to G2 are the same as meiosis except this is in a primary spermatocyte or primary oocyte
    • important to remember that S phase has occurred and gamete is 4N
  • Prophase - I
    • very long in meiosis, in spermatocyte might be days while in the oocyte it can be years or decades
    • leptotene
      • chromosome condense
    • zygotene
      • homologous chromosomes pair
      • note that this is NOT sister chromatids
      • called bivalents or tetrad in the literature
    • pachytene
      • pairing is complete
      • crossing over occurs between homologous chromosomes NOT sister chromatids
    • diplotene
      • oocytes stop here before puberty (dictyate arrest)
      • homologous chromosomes pull apart but remain attached at crossover points (chiasma)
        • note that chiasma are not the centromeres
      • RNA synthesis can occur up to this point
    • diakinesis
      • RNA synthesis stops
      • the 4 chromatids of each pair of homologous chromosomes become visible
      • homologous chromosomes remain linked at chiasma
      • chromatids are linked at centromere
  • Metaphase - I
    • nuclear membrane breaks down
    • spindles attach to centromeres
    • homologous chromosomes are initially attached at chiasma
    • homologous chromosomes go to opposite poles and then pair across from one another in the center of the metaphase plate
  • Anaphase - I
    • homologous chromosomes pull apart
    • chiasma separate
    • homologous chromosomes move to opposite poles
  • Telophase - I
    • microtubules disappear and nuclear envelopes begin to reappear
  • Cytokinesis - I
    • division to form secondary spermatocyte or secondary oocyte and polar body - I
  • Interphase - II
    • short
    • No DNA synthesis
  • Prophase - II
    • brief
  • Metaphase - II (same as mitosis)
    • oocyte stops here until ovulated and resumes only if fertilized
  • Anaphase - II (same as mitosis)
  • Telophase - II (same as mitosis)
  • Cytokinesis - II (same as mitosis)
    • results is haploid daughter cells
      • remember for oocyte this stage cell never exists because meiosis is only completed after penetration of the oocyte by a sperm

Key differences between Mitosis and Meiosis

• presence of chiasma (crossing over) in meiosis
  • leads to homologous chromosomes pulling apart in anaphase - I
• in mitosis, chromatids pull apart

Review Oogenesis

Review Spermatogenesis

Abnormalities

• Aneuploidy
  • not an exact multiple
  • can be hypo or hyper
  • example: 2N - 1 or 2N +1
• Euploidy
  • exact multiple of the haploid state
  • example: 3N, 4N etc.
• Non-disjunction
  • failure of chromosomes to separate fully at meiosis
  • causes aneuploidy and occurs in meiosis
  • example: N-1 or N+1
  • Kleinfelter's Syndrome
    • XXY
    • male, tall, small testis, low levels of androgens, low IQ, some believe these individuals have criminal tendencies
  • Turner's Syndrome
    • XO
    • female, no ovaries, small stature, remains sexually immature unless hormonal treatment
  • Down's Syndrome
    • extra copy of chromosome 21 (ie 3 chromosomes #21)
    • probability increases with age
      • at age 35, 2 per 1000 births
      • at age 40, 6 per 1000 births
      • at age 45, 16 per 1000 births

Review Questions: