Mutation as the ultimate source of new variation

Meiosis reshuffles EXISTING alleles; mutation is the only process that creates a genuinely NEW allele in the first place.

How a mutation enters, and can leave, a gene pool

A MUTATION is a random change in a DNA base sequence, which can create a brand-new allele that did not exist in the population before.
Only a mutation in a GAMETE (or a cell that produces gametes) can be passed to offspring and enter the gene pool — a mutation in a body (somatic) cell affects only that individual and is not inherited.
A NEW allele can then be gained or lost from a small population purely by CHANCE (genetic drift), independent of whether it is helpful or harmful — this is why small populations can end up with fewer harmful mutations than expected, if drift happens to remove them, or more, if drift happens to fix them.
Harmful mutations tend to accumulate MORE slowly in small, inbred populations than expected, because natural selection combined with drift can more efficiently purge them when there are fewer individuals carrying compensating variation — though drift can just as easily fix a harmful allele by chance.

Worked example Explaining why a small, inbred population lost harmful mutations rather than gaining them A population reduced to just 51 individuals, isolated and inbreeding for 10,000 years, is found to carry FEWER harmful mutations than a related, larger extinct population. Give possible reasons. NATURAL SELECTION: in a small population, harmful mutations have a bigger relative effect on fitness, so individuals carrying them may be more likely to be selected against and removed from the gene pool over many generations. GENETIC DRIFT: in a small population, ANY allele — harmful or not — can be lost purely by chance, since each individual represents a larger share of the total gene pool; some harmful alleles may simply have drifted out. FOUNDER EFFECT: the surviving population started from a small number of founders, who may simply not have carried some of the harmful mutations present in the larger source population to begin with. CONCLUSION: multiple mechanisms (selection, drift, founder effect) can all reduce harmful-mutation load in a small population — the strongest answers discuss more than one rather than picking just one. ✓ A "discuss THREE possible reasons" instruction requires genuinely separate mechanisms (not three versions of the same idea) — selection, drift and founder effect are three distinct, valid causes for exactly this pattern. ✕

Assuming small populations always accumulate MORE harmful mutations

It is tempting to assume inbreeding and small population size always make things worse, but genetic drift and stronger relative selection pressure can just as easily REMOVE harmful alleles from a small population by chance or through selection — a real example (like a small, isolated bird population with fewer harmful mutations than expected) shows the outcome is not automatic in either direction.

Mechanism	Could it explain FEWER harmful mutations in a small population?
Natural selection	Yes — stronger relative fitness effect in a small population
Genetic drift	Yes — can remove any allele, harmful or not, purely by chance
Founder effect	Yes — founders may simply never have carried it

Practice for this standard covers the whole topic — flashcards and quiz.