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 that have inhabited the mid- and high-land areas of southern Ethiopia for millennia. Using the eleven HapMap populations as the comparison group, we found Wolaita-specific signals of recent positive selection in several 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 SNPs 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.

Loci associated with skin pigmentation identified in African populations

“…1) and is a target of selection in Europeans, Central Asians and North Indians (15-17). In Africa this variant is common (28-50% frequency) in populations from Ethiopia and Tanzania with high Afroasiatic ancestry (18, 19) and is at moderate frequency (5-11%) in San and Bantu populations from Botswana with low levels of East African ancestry and recent European admixture (20, 21) (Fig. 1 and figs.…”

Genomic landscape of the signals of positive natural selection in populations of Northern Eurasia: A view from Northern Russia

“…Such SNPs were further annotated using the snpEff program (v.4.3p) [72]. Additionally, genes or genomics regions subjected to selective pressure were searched in 100 kb non-overlapping genomic windows contained SNPs found in the 0.1% tail of the empirical distribution of the test statistics [27,73,74]. Windows with two or more such SNPs were filtered and SNPs from them were annotated.…”

Examining How Our Shared Evolutionary History Shapes Future Disease Outcomes

“…Evidence shows that the APOL1 renal risk variants have increased to high frequency because their trypanolytic effect confers protection against African sleeping sickness [16]. Furthermore, significant selection signals were detected in the PPARA gene involved in energy metabolism and fat storage during prolonged food deficiency in a southern Ethiopian population sample but not in HapMap African population samples [17]. The selected haplotypes may inhibit PPARA expression, leading to increased carbohydrate oxidation and lipid storage, consistent with the dietary history of the Wolaita population, who depended on Enset , a drought-resistant food crop with high-carbohydrate and low-fat and -protein contents domesticated in Ethiopia subsequent to food deprivation 10,000 years ago [17, 18].…”

“…Furthermore, significant selection signals were detected in the PPARA gene involved in energy metabolism and fat storage during prolonged food deficiency in a southern Ethiopian population sample but not in HapMap African population samples [17]. The selected haplotypes may inhibit PPARA expression, leading to increased carbohydrate oxidation and lipid storage, consistent with the dietary history of the Wolaita population, who depended on Enset , a drought-resistant food crop with high-carbohydrate and low-fat and -protein contents domesticated in Ethiopia subsequent to food deprivation 10,000 years ago [17, 18]. These findings suggest that in some African populations, the environment has influenced the genomic architecture of those individuals which has resulted in metabolically and genetically “programming” for enhanced lipid storage.…”