Selective advantage for HbS heterozygotes in areas of malaria

Heterozygotes for the sickle cell mutation are
relatively resistant to malarial infection. Erythrocytes
of heterozygotes for the sickle cell mutation
are a less favorable environment for the
malaria parasite than those of normal homozygotes.
Thus, heterozygotes develop malaria in
a much milder form or not at all. However, this
protection is at the expense of the affected homozygotes
(HbS/HbS): although they do not
contract malaria, they suffer from the severe
hemoglobin disorder. The protection against
malaria conferred by sickle cell heterozygosity
is an advantage in regions where malaria is
common. With reduced morbidity and mortality,
heterozygotes have a higher probability of
survival and of being able to reproduce (selective
advantage). This explains the high
frequency of the sickle cell gene observed there
(see p. 168). The sickle cell mutation has arisen
independently in at least four or five different
malaria-infested regions and has subsequently
spread out in the respective populations. Sickle
cell anemia is the best example in humans of a
selective advantage in heterozygotes for a mutant
allele that leads to severe illness in the homozygous
state.