Heterozygous advantage describes the case in which the heterozygote is fitter than both homozygotes. The fitnesses can be written:
When heterozygotes are fitter than the homozygotes, 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 controversial explanations for the existance of genetic variability in natural populations.
The classic example of heterozygous advantage is sickle cell anemia where humans who are homozygotic for sickle shaped cells (pictured opposite) suffer from a near lethal condition.