Genetic Recombination and Variation

Meiosis does not simply halve chromosome number. It generates new genetic combinations at every stage. Three mechanisms, acting at three different points in the reproductive sequence, account for the extensive genetic variation between siblings and across a population.

Crossing over is the physical exchange of chromosomal segments between non-sister chromatids of a pair of homologous chromosomes. It occurs during pachytene of prophase I of meiosis, while the synaptonemal complex holds the two homologues in precise alignment.

Specific recombination protein complexes create a controlled double-strand break in the DNA of one chromatid. The break is then repaired using the aligned homologous chromatid as a template. This exchanges the corresponding segment of genetic material between the two chromatids.

The result is a chromatid that is no longer purely maternal or purely paternal along its length. It is a mosaic, carrying maternally derived alleles at some points and paternally derived alleles at others, in a pattern unique to that recombination event.

The sites of crossing over remain visible under the microscope as chiasmata from diplotene onward. On average, at least one, and often several, chiasmata form along each chromosome pair. Larger chromosomes generally show more crossover events than smaller chromosomes.

Crossing over involves homologous chromosomes: the maternally and paternally derived versions of the same chromosome exchange corresponding segments with one another. Exchange does not occur between different, non-homologous chromosomes.

The two homologues carry the same genes in the same linear order, though frequently different alleles of those genes. The exchange reshuffles which combination of maternal and paternal alleles is linked together on a single resulting chromatid. It does not alter the overall complement or order of genes.

This mechanism is the source of new allele combinations at the level of individual genes within a single chromosome. A chromosome passed on to an offspring is therefore very rarely an unaltered copy of either of that parent's two homologous chromosomes. It is typically a novel recombinant combining segments from both.

Independent assortment is the random, independent orientation of each of the 23 homologous chromosome pairs (bivalents) at the metaphase I plate. The combination of maternal and paternal chromosomes distributed to each daughter cell at the end of meiosis I is determined separately, and randomly, for every chromosome pair.

The orientation of one bivalent at metaphase I has no influence on the orientation of any other bivalent. A single individual can therefore produce 2 raised to the power of 23 theoretically distinct chromosomal combinations, over 8 million, from independent assortment alone.

This variation comes purely from the random distribution of entire, already-recombined chromosomes between daughter cells. It is independent of, and additional to, the variation generated by crossing over within each chromosome.

Random fertilisation is the essentially unpredictable pairing of one gamete from the mother with one gamete from the father. Each parent can independently produce a very large number of genetically distinct gametes through the combined effects of crossing over and independent assortment.

Each parent can theoretically produce over 8 million genetically distinct gamete combinations from independent assortment alone, before accounting for crossing over. The number of genetically distinct zygotes possible from a single couple is therefore astronomically large, comfortably exceeding the total number of humans who have ever lived.

This is the mechanistic reason that full, non-twin siblings, despite sharing the same two parents, are never genetically identical to one another.

Crossing over, independent assortment and random fertilisation operate sequentially and cumulatively rather than in isolation.

• Crossing over first reshuffles allele combinations within individual chromosomes during prophase I.
• Independent assortment then randomly distributes these already-recombined chromosomes between gametes during metaphase I.
• Random fertilisation finally combines one such gamete from each parent to form the zygote.

Each mechanism multiplies, rather than simply adds to, the variation generated by the mechanisms before it. This is why the combined genetic diversity generated by meiosis and fertilisation so fully exceeds what any single mechanism could achieve on its own.