The population genetics of alpha-thalassemia and the malaria hypothesis.

Abstract

Since the advent of rapid DNA analysis techniques, surveys of numerous tropical and subtropical regions have revealed remarkably high frequencies of α-thalassemia. Indeed, it now appears that α+-thalassemia, which leads to decreased α-globin production by an affected chromosome, is the commonest single gene disorder in man (Higgs and Weatherall 1983). The finding of β-thalassemia in areas that were or had been malarious prompted Haldane (1949) to suggest that thalassemia heterozygotes might enjoy increased fitness in the presence of this parasitic disease. Epidemiological and in vitro studies on sickle cell carriers subsequently provided convincing support for the malaria hypothesis as applied to the hemoglobinopathy Hb S (for review, see Allison 1965; Pasvol and Wilson 1982). However, for β-thalassemia there is only limited evidence from the geographical distribution of this condition to support the hypothesis. In the case of the common mild forms of α+-thalassemia there is no evidence that malarial selection...