Positive Selection Scans Identified Immune System and Lactose Tolerance Haplotypes in a Middle Eastern Population

Archaeological evidence suggests that the Middle East played an important role during the dispersal of modern humans out of Africa. In an attempt to explore natural selection in the region, we analyzed 662,750 variants in 583 Middle Eastern individuals. Using this data, we searched for areas in the genome that show signatures of positive selection in this population using a new approach, Ohana, which estimates deviations from genome-wide ancestral admixture components. Our results identified hundreds of single nucleotide variants across the genome that presented strong signals of positive selection. In general, these variants that have evolved under putative positive selection are clustered around haplotypes associated with blood and immune system-related phenotypes, arguably as a response mechanism to common pathogens in the region, including malaria. The highest concentration of variants was found in a roughly 2.5 million bases region in Chromosome 2. This region harbors a total of 14 genes, including the LCT gene, which was previously associated with lactose tolerance. We identified two variants to be evolving under putative positive within the LCT gene and further showed that these variants have higher allele frequency in the Middle Eastern populations as compared to other populations across the globe. Our results contribute to the notion that local adaptive forces in the last 10,000 years may have shaped human genetic variation.