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.