Adaptations will often be imperfect because of genetic constraints. An example of such a constraint occurs when the heterozygote at a locus has a higher fitness than either homozygote, and the population evolves to an equilibrium at which all three genotypes are present. A proportion of the population must therefore have the deleterious homozygous genotypes.

This situation arises because the heterozygotes cannot, under Mendelian inheritance, produce purely heterozygous offspring: they cannot breed true. Insofar as heterozygous advantage exists, some members of the natural populations will be imperfectly adapted. The importance of heterozygous advantage is controversial; but there are undoubted examples, such as sickle cell anemia - caused by sickle shaped blood cells, pictured opposite - which is a practical example of imperfect adaptation due to a genetic constraint.