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

The Tibetan Mastiff (TM) is a native of the Tibetan Plateau, which has acquired fast adaption to the extreme highland environment. Recently, the impact of positive selection on the genome of Tibetan Mastiffs has been studied and potential hypoxia-adaptive genes have been identified. However, the origin of the adaptive variants remains unknown. In this study, we investigated the signature of genetic introgression on the adaption of TMs for the highland environment with the genomic data of dogs and wolves from the high and low altitudes. Using the method of 'ABBA/BABA' test, we identified genomic regions of TM possibly introgressed from grey wolves living in the Tibetan Plateau. Several of the regions including the EPAS1 and HBB loci also showed 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 on all available canid genomes. The estimated time of introgression based on a non-coding region of the EPAS1 locus was consistent with the history of the initial colonization of the Tibetan Plateau by modern humans. Our results demonstrated that adaptive introgression of wolves from the highland plays an important role for the TMs living in the hypoxic environment, which indicated that domestic animals could acquire local adaption quickly by secondary contact with their wild relatives.