Genetic Mechanism Of High-altitude Adaptation In Tibet Dog

Hypoxic environment represents one of the most extreme environmental challenges for both human beings and animals living at high altitudes. Previous studies on the Tibetan, Andean and high-altitude Ethiopian human populations have revealed distinct genetic components, different physical characteristics and signatures of selection for hypoxia adaptation. Meanwhile, As the first domesticated animal and developed an intimate relationship with human beings, domestic dog has followed human beings and adapted the high-altitude hypoxic ecological niches with us. However, the studies in dogs are quite incomplete.Here, we first measured the hemoglobin levels in Tibetan dogs and village dogs from Chinese low lands. We found that the average hemoglobin levels are very similar between these two groups, these physiological characterized is quite similar to Tibetan, suggesting that dogs in Tibet might share similar adaptive strategies as the human in Tibet. Through a whole-genome sequencing approach,2.4million high quality single nucleotide polymorphisms (SNPs) were extracted. By a set of stringent criteria, we performed F statistic(Fst) and Fisher’s exact test and have successfully identified EPAS1and HBB as candidate genes for the high-altitude hypoxic adaption on the Tibetan plateau. The population genetic analysis shows a significant convergence pattern between humans and dogs in Tibet. The similarities candidate loci that exhibit putative signatures of positive selection and the physiological traits of hemoglobin levels between humans and dogs in the same environment, but not similar between human populations in different regions. These conclusions collectively seem to suggest that an extraordinary landscape of convergent evolution between humans and dogs in the Tibetan plateau.Moreover, based on the successfully identified EPAS1and HBB as candidate genes for high-altitude adaption from the above findings, we explored the candidate non-synonymous mutations in the two most prominent genes, EPAS1and HBB in large population size and sampling coverage from sea level to the Qinghai-Tibetan Plateau across a continuous gradient of altitudes in China. For the four non-synonymous mutations in EPAS1and two non-synonymous mutations in HBB, there is a significant positive linear correlation between increased altitude and the frequency of the mutant allele in Chinese indigenous dogs. These results strengthen the conclusion of our previous research conclusion that HBB and EPAS1exert a positive effect on high-altitude hypoxic adaptation in dogs.