Investigate the causes of genetic variation relating to the changes and conservation of the DNA sequence including: variations in gametes due to crossing over and segregation in meiosis, the cell replication processes that allow the conservation, variation and mutation of DNA, and the contribution of mutation to genetic variation and evolution

What this dot point is asking

NESA wants you to explain where genetic variation comes from: the shuffling that happens in meiosis, the fidelity of DNA replication, and the role of mutation as the ultimate source of new alleles. The evolutionary significance ties Modules 5 and 6 together.

The answer

Genetic variation has two distinct sources: recombination of existing alleles in meiosis and fertilisation, and new alleles introduced by mutation.

Variation from meiosis

Meiosis produces haploid gametes from a diploid parent, reducing chromosome number by half. Three processes generate variation.

1. Independent assortment. During metaphase I, the homologous chromosome pairs line up at the spindle equator independently of one another. Either the maternal or the paternal chromosome of each pair can face either pole. With $n$ chromosome pairs, this produces $2^n$ possible combinations. In humans (n = 23), that is $2^{23}$ = 8,388,608 combinations per gamete.

2. Crossing over. During prophase I, homologous chromosomes pair up (synapsis) and exchange segments at chiasmata. This recombines maternal and paternal alleles within each chromosome, generating combinations that were not present in either parent. Crossing over essentially makes the $2^n$ figure an underestimate; the actual number of unique gametes is astronomically larger.

3. Random fertilisation. Any one of the millions of possible sperm can fertilise any one of the possible eggs, multiplying the variation across the population.

These mechanisms generate enormous variation within a generation, but they all act on existing alleles. They cannot create alleles that are not already present in the parents.

Variation from DNA replication and conservation

Semi-conservative replication. Each daughter DNA molecule retains one original strand and one newly synthesised strand. This conserves the parental sequence.

Proofreading. DNA polymerase has a 3' to 5' exonuclease activity that removes incorrectly added bases during synthesis, reducing the error rate from about 1 in $10^5$ (unaided) to 1 in $10^7$.

Mismatch repair. After replication, mismatch repair proteins recognise base mismatches and excise the wrongly inserted base, reducing the error rate further to about 1 in $10^{10}$.

The net effect is that DNA replication is extraordinarily faithful. This conservation is essential for maintaining the genetic information across generations and across the trillions of cell divisions within a single body.

Variation from mutation

Even with proofreading and repair, mistakes accumulate. Mutagens (UV, chemicals, viruses) further increase the rate. In humans, each newborn carries roughly 60 to 100 new mutations not present in either parent. Most are in non-coding regions and have no effect; some are mildly deleterious; a small fraction are advantageous.

Mutation is the only source of completely new alleles. Meiosis can only shuffle what already exists.

The link to evolution

Natural selection requires three things: heritable variation, differential reproduction and inheritance of the advantageous variant.

• Meiosis generates the variation natural selection acts on in the short term.
• Mutation supplies new alleles for selection to act on in the long term.
• Selection, drift and gene flow then change allele frequencies across generations.

Without mutation, evolution would stall once the existing alleles were sorted by selection. With mutation, the genetic toolkit is continually replenished and new traits (and new species) can arise.

Summary table

Worked example

A population of beetles in a forest is genetically uniform in colour because all individuals carry only the "green" allele. The forest is gradually replaced by darker bark.

Without mutation. Meiosis can shuffle the chromosomes, but every gamete still carries only the green allele. The population cannot adapt to the darker environment.

With mutation. A rare mutation produces a "brown" allele. On the new dark bark, brown beetles are camouflaged and survive predation better. The brown allele rises in frequency over generations. Selection acts on the new allele introduced by mutation, producing adaptive evolution.

This is the standard model of how mutation supplies the raw material for natural selection.

Conservation and variation: a balance

A genome that mutates too much loses its information; a genome that mutates too little cannot adapt. Real organisms balance the two with high-fidelity replication (conservation) plus a small residual rate of mutation (variation). The mutation rate is itself an evolved property.

Common traps

Saying meiosis creates new alleles. It does not. Meiosis recombines existing alleles into new combinations; only mutation creates new alleles.

Forgetting random fertilisation. It is a separate source of variation distinct from independent assortment and crossing over.

Saying DNA replication is "perfect." It is extremely faithful (1 in $10^{10}$) but not perfect. The residual errors are an essential source of new alleles.

Treating mutation as always harmful. Most mutations are neutral; some are mildly deleterious; a small fraction are beneficial. The beneficial ones drive adaptive evolution.

Skipping the evolutionary link. This dot point explicitly asks for the link to evolution; not making it loses marks.

In one sentence

Genetic variation arises from meiosis (independent assortment, crossing over and random fertilisation, which shuffle existing alleles) and from rare DNA replication errors and mutagens (which introduce new alleles), so DNA replication conserves the genome while mutation supplies the new variation that natural selection acts on across generations, driving evolution.