Tracing the origin of sickle cell disease back to 50,000 years. Open Access

Sickle cell disease (SCD) is a genetic disorder resulting from a mutation in the hemoglobin beta (HBB) gene and is predominantly found in malaria-endemic regions of sub-Saharan Africa and India. This review explores the origin and dissemination of SCD, hypothesizing its emergence in Africa 50,000 years ago under selective pressure from malaria. The movement of Homo sapiens to occurred 50,000 years ago. Migrating Homo sapiens are theorized to have transported the mutation via the eastern coastal route, passing through the Arabian Peninsula into India. The prevalence of the Arab–Indian haplotype en route in endemic regions supports this theory, linking SCD propagation to early human migratory patterns. Genetic evidence reveals that tribal populations in central India, which practice endogamy, harbor the Arab–Indian haplotype with a high prevalence of SCD This overlap of haplotype distributions between Africa, the Arabian Peninsula, and India underscores the evolutionary advantage of SCD in malaria-endemic zones. This well-documented evidence strengthens our proposed hypothesis that the origin of SCD occurred 50,000 years ago in Africa and spread to India via the Arabian Peninsula, providing protection from malaria to date.