Nuclear Structure and Function Research Group

Objectives
The material covered in this lecture, coupled with the recommended reading, should enable you to:
• understand the concept of a cell cycle
• describe the processes of mitosis and meiosis, and the essential differences between them
• understand that recombination allows genes to be shuffled, so new combinations can be tested by evolution.

Mitotic cycle
During interphase, chromatin forms dense mass, but during cell division (mitosis) condenses into discrete chromosomes (Fig). Mitosis divides parental cell equally between 2 daughters; mitochondria and vesicles derived from ER segregate randomly, chromosomes precisely.
Cell cycle (Fig): G1, S (Fig), G2, M (Fig). G0 (non-dividing, differentiated, cells); programmed cell death, apoptosis; S originally recognized using [³H]thymidine; M visible in LM (nuclear membrane breaks down, chromatin condenses into chromosomes, attach to spindle containing tubulin (Fig), segregated accurately by spindle, contractile ring (actin) pinches cell in two; Fig). Spindle inhibitors (Fig). M divided: pro-, meta-, ana- (A and B), telo-phase (Fig).
Metaphase chromosome: 2 chromatids, centromere (spindle, correct segregation), telomere (Fig).
Classify: metacentric (centromere in middle), acrocentric (towards one end), telocentric (at end). Alternatively: sex + autosomes (44 autosomes + 2 X in female, or 1 X + 1 Y in male). Karyotype (46 in human, 40 in mouse; Fig).
Centrosome - densely-staining pair of centrioles surrounded by amorphous matrix (Fig); radiating microtubules (microtubule organizing center, aster); split and moves during cycle (Fig); some tubules catch centromeres, then spindle pulls apart the 2 chromosome sets.

Meiotic cycle (Fig)
Somatic cell - diploid (2n) amount of DNA in G1, tetraploid (4n) in G2. Sexual reproduction: production of haploid (1n) gametes during meiosis, fusion of 2 gametes to give (2n) zygote. DNA of 2n cell duplicated, then 2 successive nuclear divisions generate 4 haploid gametes. Fertilization restores diploidy. So alternation of haploid + diploid generations. In most higher organisms, haploid phase brief.
Two features meiosis ensure haploid generation receives mixed set genes (increased genetic variation): (i) segments homologs exchanged (recombined) randomly, (ii) maternal/paternal homologs assorted (segregated) semi-randomly at 1st division (Fig). New gene combinations tested by evolution - fit survive/reproduce, less fit culled.
Meiosis as 3-stage process: DNA of 2n cell replicated to generate chromosomes with attached chromatids in 4n cell, chromosomes divided among 4 haploid cells by consecutive divisions (meiosis I, II). During I (reductional division), homologs pair, segregate (pairing required for proper segregation). During II (equational division), sisters segregated.
Almost invariably, each of resulting 4 haploid cells differs genetically from other 3. Variability arises because (i) new variants generated by recombination, (ii) chromosomal set split semi-randomly among haploid cells, and (iii) additional variation introduced during fertilization when different male/female gametes fuse; therefore, each diploid egg carries unique set genes. First source of variation arises from high levels of homologous recombination that occur during I. Bivalent, join (chiasma, chiasmata; Fig). Second source discovered by Mendel - semi-random segregation that occurs during I (segregation not random in that each haploid cell eventually receives only 1 copy of each homolog, but completely random in that different homologs segregate independently; Fig).
Stages of I. Prophase (can occupy 90% meiosis) when duplicated chromosomes partially condense to become visible as chromosomes, dance, 'feel' among crowd for partners. Once partners identified (leptotene), homologs pair or synapse (zygotene), tightly align (synaptonemal complex during pachytene; Fig), unpair (desynapse during diplotene) and move apart (diakinesis; Fig). When I ends, cells in many organisms pass quickly through II. No DNA made during this interval, and II similar to mitosis, except only 1 (duplicated) copy of each chromosome present.

Recombination
Important roles in most cells (eg in bacteria, main role enables replicating complex to bypass lesion in parental strand by exchanging daughter templates), but central role in meiosis (rate >1000x that in mitotic cycle).
Meiotic recombination: DNA sequence exchanged between homologs, shuffling of different versions of genes (alleles) so new combinations tested by evolution. Different organisms use different pathways, share principles (Fig):
(i) 2 homologous DNA duplexes cross-over (double helices break, broken ends join). (ii) Initiation: homology search (DNA-DNA pairing). (iii) Gives staggered heteroduplex joint (strand in one duplex paired with complementary strand in other) - key X-shaped Holliday junction (Fig), branch migration (Fig). (iv) Cleavage/rejoining generally precise, so sequence at point of exchange remains unchanged (reciprocal v non-reciprocal recombination). (iv) Overall effect is to move genes between homologs, without normally changing relative positions on chromosome.

References
Ch 17, 21 in Alberts, B. et al. (2014). 'Molecular Biology of the Cell'. 6th Ed. Garland [see also PubMed].
Hochwagen, A. (2008). Meiosis. Curr. Biol. 18, R641-645. [PubMed]

Top | Home | Maintained by Peter Cook |