Evolution of the hemoglobin S and C genes in world populations.

A polymorphic HpaI endonuclease recognition site on the 3' side of the beta-globin gene was used to analyze the evolution of the beta-globin gene mutants S and C. Study of the world wide distribution of the normal and variant HpaI sites showed that the mutation which resulted in the variant 13.0-kilobase fragment arose in a localized region in West Africa. It predated the hemoglobin S and C mutations, both of which arose separately from a chromosome with the variant 13.0-kilobase HpaI site. In contrast, the sickle genes in other parts of Africa and in Asia are associated with the normal 7.6-kilobase HpaI fragment, indicating that the sickle mutations in these other areas arose separately from that in West Africa.