title: Novel genomic signals of recent selection in an Ethiopian population.
abstract: 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.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Fasil
authors.initials: F
authors.lastname: Tekola-Ayele
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors.forename: Elena
authors.initials: E
authors.lastname: Hailu
authors.affiliation: Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
authors.forename: Abraham
authors.identifier: 0000000280281150
authors.initials: A
authors.lastname: Aseffa
authors.affiliation: Brighton and Sussex Medical School, Falmer, Brighton, UK.
authors.forename: Gail
authors.identifier: 0000000327967468
authors.initials: G
authors.lastname: Davey
authors.affiliation: Brighton and Sussex Medical School, Falmer, Brighton, UK.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Newport
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Charles N
authors.identifier: 000000015759053X
authors.initials: CN
authors.lastname: Rotimi
mesh_terms: D017920:Antiporters / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D004604:Elephantiasis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism / Q000235:genetics; D005002:Ethiopia; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D015234:HLA-A Antigens / Q000235:genetics; D060148:HapMap Project; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics / Q000473:pathology; D047493:PPAR alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D012880:Skin Pigmentation / Q000235:genetics; D012359:tRNA Methyltransferases
chemical_list: D017920:Antiporters; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D015234:HLA-A Antigens; C485559:NEGR1 protein, human; D047493:PPAR alpha; C506584:SLC24A5 protein, human; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human