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The recent feasibility of genome-wide studies of adaptation in human populations has provided novel insights into biological pathways that have been affected by adaptive pressures. However, only a few African populations have been investigated using these genome-wide approaches. Here, we performed a genome-wide analysis for evidence of recent positive selection in a sample of 120 individuals of Wolaita ethnicity belonging to Omotic-speaking people who have inhabited the mid- and high-land areas of southern Ethiopia for millennia. Using the 11 HapMap populations as the comparison group, we found Wolaita-specific signals of recent positive selection in several human leukocyte antigen (HLA) loci. Notably, the selected loci overlapped with HLA regions that we previously reported to be associated with podoconiosis-a geochemical lymphedema of the lower legs common in the Wolaita area. We found selection signals in PPARA, a gene involved in energy metabolism during prolonged food deficiency. This finding is consistent with the dietary use of enset, a crop with high-carbohydrate and low-fat and -protein contents domesticated in Ethiopia subsequent to food deprivation 10 000 years ago, and with metabolic adaptation to high-altitude hypoxia. We observed novel selection signals in CDKAL1 and NEGR1, well-known diabetes and obesity susceptibility genes. Finally, the SLC24A5 gene locus known to be associated with skin pigmentation was in the top selection signals in the Wolaita, and the alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) associated with light skin pigmentation in Eurasian populations were of high frequency (47.9%) in this Omotic-speaking indigenous Ethiopian population.

Novel genomic signals of recent selection in an Ethiopian population