Meiosis: special cell division for production of gametes (sex cells). Results in: 4 haploid (n) cells from 1 diploid (2n) cell. Two consecutive divisions: Meiosis I (reductional division, separates homologous chromosomes, 2n → 2n but split into 2 cells each = n with 2 chromatids each) and Meiosis II (equational division, separates sister chromatids, like mitosis, 2(n) → 4(n)). Key features: Homologous chromosome pairing (synapsis) only in meiosis. Crossing over (genetic recombination) only in meiosis. Unique prophase I stages (LZPDD). Two rounds of division with no DNA replication between them. Reduction of chromosome number from diploid (2n) to haploid (n). Significance: produces genetic variation (crossing over + random assortment). Maintains species chromosome number across generations (meiosis halves, fertilisation doubles). Location: gonads (ovaries and testes in animals); anthers and ovules in plants.

Prophase I is the longest phase of meiosis (can last days to years depending on organism). Substages (remember: LZPDD): Leptotene (thin threads): chromosomes begin condensing, become visible as thin threads. Two sister chromatids of each chromosome held together. Zygotene (joined): homologous chromosomes begin to pair (synapsis) → bivalent (tetrad = 4 chromatids). Synaptonemal complex (protein framework) forms between homologous chromosomes. Pachytene (thick): crossing over occurs! Synaptonemal complex fully formed. Non-sister chromatids of homologous chromosomes exchange segments at chiasmata. Molecular machinery: Spo11 creates double-strand breaks → Dmc1/Rad51 recombinases → strand invasion → Holliday junction → resolution. Diplotene (two threads): synaptonemal complex dissolves. Bivalents held together only at chiasmata. Oocytes of many animals arrested here (sometimes for years — human oocytes arrested from foetal life until ovulation!). Diakinesis (moving apart): chromosomes maximally condensed. Terminalization of chiasmata (chiasmata move to chromosome ends). Nuclear envelope breaks down. Meiosis I proceeds.

Metaphase I: bivalents line up on metaphase plate. Each bivalent is pulled by spindle fibres from opposite poles. Random orientation of maternal/paternal chromosomes → independent assortment. Anaphase I: homologous chromosomes (each still consisting of 2 sister chromatids) separate to opposite poles. Sister chromatids remain joined at centromere. Cohesin on chromosome arms cleaved (by separase) but centromeric cohesin protected by shugoshin. Telophase I: two groups of haploid chromosomes (each chromosome with 2 chromatids). Nuclear envelope may reform. Cytokinesis → 2 secondary spermatocytes (or 1 secondary oocyte + 1 first polar body). Interkinesis: short period between meiosis I and II. NO S phase (no DNA replication). Chromosome number has been reduced: each cell has n chromosomes, each composed of 2 sister chromatids.

Meiosis II resembles mitosis but starts with haploid cells. Prophase II: chromosomes condense (if reformed in interkinesis). Metaphase II: chromosomes line up at metaphase plate (n chromosomes, each with 2 chromatids). Anaphase II: centromeric cohesin cleaved → sister chromatids separate to opposite poles. Telophase II: 4 haploid cells form. Cytokinesis → 4 haploid cells (n chromosomes, each with 1 chromatid = 1 DNA molecule). Spermatogenesis: 4 functional spermatids (each develops into sperm). Oogenesis: unequal division → 1 large secondary oocyte + 1 first polar body (meiosis I), then 1 ovum + 1 second polar body (meiosis II), 1st polar body may or may not divide. Total: 1 large ovum + 2-3 small non-functional polar bodies.

Mitosis: occurs in somatic (body) cells. One division → 2 daughter cells. Daughter cells are diploid (2n), genetically identical to parent. No synapsis, no crossing over, no homologous pairing. Interphase S phase before every mitosis. Purpose: growth, repair, asexual reproduction. Meiosis: occurs in germ cells (gonads). Two divisions → 4 daughter cells. Daughter cells are haploid (n), genetically different. Synapsis and crossing over in prophase I. Only one S phase before both divisions. Purpose: sexual reproduction, generates genetic variation. Key distinction: in meiosis I, HOMOLOGOUS CHROMOSOMES separate (unlike mitosis where SISTER CHROMATIDS separate). This is the reductional division. Meiosis II = equational (like mitosis but from haploid cells).

Cell cycle: G1 (growth, protein synthesis) → S (DNA synthesis/replication) → G2 (growth, preparation for division) → M (mitosis/meiosis + cytokinesis). G0: quiescent state (non-dividing cells: neurons, muscle cells). Checkpoints: G1/S checkpoint (restriction point): is the cell large enough? Is DNA undamaged? G2/M checkpoint: is DNA replication complete? Are any DNA damage present? Metaphase checkpoint (spindle assembly checkpoint): are all kinetochores attached to spindle fibres? Cyclins and CDKs: regulate progression through cell cycle. Cyclin levels oscillate. CDK (cyclin-dependent kinase) active only when bound to cyclin. MPF (Maturation Promoting Factor = cyclin B/CDK1): drives entry into mitosis. Cancer: uncontrolled cell division due to loss of checkpoint control (mutations in proto-oncogenes → oncogenes, or tumour suppressor genes → non-functional).

Genetic recombination by crossing over: (1) Produces new combinations of alleles not present in parents → genetic variation → raw material for evolution. (2) Allows genes on same chromosome to assort independently (if far enough apart). (3) Provides physical connection (chiasma) between homologous chromosomes during metaphase I → essential for proper chromosome segregation (prevents non-disjunction). (4) One crossover between two genes: 50% recombinant gametes. Two crossovers (double crossover): lower apparent recombination (parental types restored). Interference: occurrence of one crossover reduces probability of adjacent crossover. Coefficient of coincidence = observed double crossovers / expected. Interference = 1 - C.O.C. Positive interference (usual): first crossover reduces probability of second nearby. Negative interference: first increases probability of second (rare).

Three mechanisms generate genetic variation during meiosis: (1) Independent assortment of homologous chromosomes (metaphase I): random orientation → $2^{23}$ possible combinations in humans (23 pairs of homologs). (2) Crossing over (prophase I): new combinations of alleles within chromosomes → even more variation. Average 1-3 crossovers per chromosome per meiosis in humans. (3) Random fertilisation: $2^{23} \times 2^{23} = \sim 7 \times 10^{13}$ possible zygote combinations (before even considering crossing over). Together: meiosis + sexual reproduction ensure that each individual (except identical twins from same zygote) is genetically unique. This uniqueness is the basis of: DNA fingerprinting (forensics), paternity testing, individual immune responses, transplant compatibility, evolution through selection on genetic variation.