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Several human genetic disorders of hemoglobin have risen in frequency because of the protection they offer against death from malaria, sickle-cell anemia being a canonical example. Here we address the issue of why this highly protective mutant, present at high frequencies in subSaharan Africa, is uncommon in Mediterranean populations that instead harbor a diverse range of thalassemic hemoglobin disorders. We demonstrate that these contrasting profiles of malaria-protective alleles can arise and be stably maintained by two well-documented phenomena: an alleviation of the clinical severity of alpha- and beta-thalassemia in compound thalassemic genotypes and a cancellation of malaria protection when alpha-thalassemia and the sickle-cell trait are coinherited. The complex distribution of globin mutants across Africa and the Mediterranean can therefore be explained by their specific intracellular interactions.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





21242 - 21246


Africa, Anemia, Sickle Cell, Epistasis, Genetic, Gene Frequency, Hemoglobins, Abnormal, Humans, Malaria, Mediterranean Islands, Thalassemia