https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430617/
>A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using single nucleotide polymorphism 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 that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and 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 with regional DNA methylation changes in TBX15
>The other region contains WARS2 and TBX15, located on chromosome 1. WARS2 encodes the mitochondrial tryptophanyl-tRNA synthetase. TBX15 is a transcription factor from the T-box family and is a highly pleotropic gene expressed in multiple tissues at different stages of development. It is required for skeletal development and deletions in this gene cause Cousin syndrome, whose symptoms include craniofacial dysmorphism and short stature. TBX15 also plays a role in the differentiation of brown and brite adipocytes. Brown and brite adipocytes produce heat via lipid oxidation when stimulated by cold temperatures, making TBX15 a strong candidate gene for adaptation to life in the Arctic. SNPs in or near both of these genes have also been associated with numerous phenotypes in GWAS studies – in particular waist-hip ratio and fat distribution in Europeans and ear morphology in Latin Americans.
>Multiple studies have shown extensive introgression of DNA from Neanderthals and Denisovans into modern humans. Many of the introgressed tracts have been shown to be of functional importance and may possibly be examples of adaptive introgression into humans, including several genes involved in immunity, several genes associated with skin pigmentation, and EPAS1, associated with high-altitude adaptation in Tibetans. Archaic humans have been hypothesized to be adapted to cold temperatures. Therefore, in this paper we examine if any of the selected genes in Inuit1 may have been introduced into the modern human gene pool via admixture from archaic humans, i.e. Neanderthals or Denisovans. We will show that the WARS2/TBX15 haplotype of high frequency in Greenlandic Inuit was likely introgressed from an archaic human population that was closely related to Denisovans. We will also show that the selection affecting this haplotype is relatively old, resulting in a high allele frequency in other New World populations and intermediate allele frequencies in East Asia. Finally, functional genomic analyses suggest that the selected archaic haplotype may affect the regulation of expression of TBX15 and WARS2, and is associated with phenotypes related to body fat distribution.