Abstract
A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using SNP chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype introgressed from an archaic population most closely related to Denisovans. The region contains two genes, WARS2 and TBX15, and has previously been associated with body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and is associated with BMI-adjusted waist circumference. We also find that in this region both the Denisovan and individuals homozygous for the introgressed allele display differential DNA methylation.
