Our results also provide some suggestions as to where the three clusters might have originated. Two splits occurred early in the original βS-carrying population. The first split defined one cluster containing HAP1 and accounting for the Cameroon and CAR haplotypes. It is plausible that HAP1 was carried from an area in or around present-day Cameroon to the area that is presently the CAR, as well as to areas east and south, as part of the Bantu expansions. However, the Bantu expansions did not extend west and north. The second split subsequently separated the clusters containing HAP16 and HAP20, the modal haplotypes accounting for the Benin and Senegal haplotypes, respectively. HAP16 and HAP20 shared one derived mutation, consistent with an early split. Furthermore, given the subsequent accumulation of derived mutations not shared between HAP16 and HAP20, effectively no gene flow occurred between these two descendant populations, consistent with geographic separation. We therefore hypothesize that the common ancestor of these two clusters existed north of Cameroon among non-Bantu-speaking peoples in or around present-day Nigeria. From this common ancestral population, a group of migrants separated and traveled west and north to the area around present-day Senegal and the Gambia. These migrants could have taken a coastal or an inland route. The finding that the Senegal haplotype was the predominant haplotype in the sample of Mende from Sierra Leone is consistent with a coastal route. We do not have data to investigate an inland route, but we note that the frequency of the sickle allele is higher along the coast than inland.53