The high frequency of sickle cell anemia in some human populations is the classic example of heterozygous advantage.

Sickle shaped blood cells (pictured opposite) are a near fatal genetic condition which is still maintained at a high frequency in certain populations. The concept of heterozygous advantage explains why.

Heterozygous advantage describes the case in which the heterozygote is fitter than both. The fitnesses can be written:

When heterozygotes are fitter than the homozygotes, therefore, natural selection will maintain a polymorphism. The result was first proved by Fisher in 1922 and independently by Haldane.

Heterozygous advantage is one of several possible explanations for the existence of genetic variability in natural populations.