Genomic Analysis Reveals Hypoxia Adaptation in the Tibetan Mastiff by Introgression of the Gray Wolf from the Tibetan Plateau.

The Tibetan Mastiff (TM), a native of the Tibetan Plateau, has quickly adapted to the extreme highland environment. Recently, the impact of positive selection on the TM genome was studied and potential hypoxia-adaptive genes were identified. However, the origin of the adaptive variants remains unknown. In this study, we investigated the signature of genetic introgression in the adaptation of TMs with dog and wolf genomic data from different altitudes in close geographic proximity. On a genome-wide scale, the TM was much more closely related to other dogs than wolves. However, using the 'ABBA/BABA' test, we identified genomic regions from the TM that possibly introgressed from Tibetan gray wolf. Several of the regions, including the EPAS1 and HBB loci, also showed the dominant signature of selective sweeps in the TM genome. We validated the introgression of the two loci by excluding the possibility of convergent evolution and ancestral polymorphisms and examined the haplotypes of all available canid genomes. The estimated time of introgression based on a non-coding region of the EPAS1 locus mostly overlapped with the Paleolithic era. Our results demonstrated that the introgression of hypoxia adaptive genes in wolves from the highland played an important role for dogs living in hypoxic environments, which indicated that domestic animals could acquire local adaptation quickly by secondary contact with their wild relatives.