In the Arctic, the Inuits have adapted to cold and a seafood diet. After the first genomic analysis of Greenlandic Inuits, a region in the genome containing two genes (TBX15 and WARS2) has now been scrutinized by researchers.
Dr. Fernando Racimo of the New York Genome Center and his colleagues have now followed up on that study to trace back the origins of these adaptations.
“To identify genes responsible for biological adaptations to life in the Arctic, Fumagalli et al. scanned the genomes of Greenlandic Inuit using the population branch statistic, which detects loci that are highly differentiated from other populations,” the researchers explained.
“Using this method, they found two regions with a strong signal of selection: (i) one region contains the cluster of FADS genes, involved in the metabolism of unsaturated fatty acids; (ii) 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.”
“TBX15 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.”
In their own study, Dr. Racimo and co-authors used the genomic data from nearly 200 Greenlandic Inuits and compared this to the 1000 Genomes Project and ancient DNA from Neanderthals and Denisovans.
The results provide convincing evidence that the Inuit variant of the TBX15/WARS2 region first came into modern humans from an archaic hominid population, likely related to the Denisovans.
“The Inuit DNA sequence in this region matches very well with the Denisovan genome, and it is highly differentiated from other present-day human sequences, though we can’t discard the possibility that the variant was introduced from another archaic group whose genomes we haven’t sampled yet,” Dr. Racimo said.
The scientists found that the variant is present at low-to-intermediate frequencies throughout Eurasia, and at especially high frequencies in the Inuits and Native American populations, but almost absent in Africa.
They speculate that the archaic variant may have been beneficial to modern humans during their expansion throughout Siberia and across Beringia, into the Americas.
The team also worked to understand the physiological role of the TBX15/WARS2 region.
They found an association between the archaic region and the gene expression of TBX15 and WARS2 in various tissues, like fibroblasts and adipose tissue.
They also observed that the methylation patterns in this region in the Denisovan genome are very different from those of Neanderthals and present-day humans.
“All this suggests that the introduced variant may have altered the regulation of these genes, thought the exact mechanism by which this occurred remains elusive,” Dr. Racimo said.
The team’s results were published online this week in the journal Molecular Biology and Evolution.
Fernando Racimo et al. Archaic adaptive introgression in TBX15/WARS2. Mol Biol Evol, published online December 21, 2016; doi: 10.1093/molbev/msw283