Origin of Sickle Gene

"Initially the single mutation theory was postulated in which it was conveyed that a single mutation occurred in Neolithic times in the then fertile Arabian Peninsula. Then, the changing climatic conditions and conversion of this area to a desert caused the migration of people that could have carried the gene to India, Eastern Saudi Arabia and down to Equatorial Africa. This hypothesis was supported by citing the distribution of certain agricultural practices and anthropological evidences.

But it is now quite clear that the sickle cell mutation has occurred as several independent events. By using a series of different restriction endonucleases, different chromosome structures (haplotypes) are identified and Hb S gene has been found to be linked to certain commonly occurring haplotypes that are generally different from those bearing the Hb A gene.

In Africa the Hb S gene is associated with at least three haplotypes representing independent mutations. They are the Benin haplotype, the Senegal haplotype and the Central African Republic or the Bantu haplotype found in the central west Africa, the African west coast and the Central Africa (Bantu speaking Africa) respectively. A fourth haplotype, the Asian haplotype is found in the eastern province of Saudi Arabia and central India.

It appears that the sickle cell mutation has occurred on at least three occasions in the African continent and at least once in either the Arabian Peninsula or the Central India and from the primary sites the migration to the other regions has occurred. This can explain the observation made by many investigators that there is wide spread chromosomal heterogeneity of Bs gene cluster haplotypes in United States as compared to the homozygous condition in Africa, Arab or Asia. The slaves with sickle cell trait who were exported from various parts of Africa to United States had the specific Bs gene haplotype found in their region but after arrival in US, Jamaica and Brazil, over the years there have been considerable admixture of African ethnic groups. Available calculations suggest that this gene has developed between 3000 and 6000 generations, approximately 70000-150000 years ago."