Gene Introgression From Tibetan Grey Wolf Into Tibetan Mastiff

It is a great challenge for the creature living in the low oxygen,low pressure,low temperatoe and intensive ultraviolet radiation environment of high altitude localities.During the past few years,adaptation of the humans and the animals living in plateau is a topic of the most ardent research.Tibetan Mastiffs,an ancient breed dog,have adapted to low oxygen environment in the Tibetan plateau.Tibetan Mastiff is well known for unique characteristics and is a popular breed dog for the research relating to plateau adaptability.It is not clear whether there exits gene flow at the genome level between Tibetan mastiff and Tibetan wolf,so we do a research about the issue.To investigate the above questions,we downloaded the published genomic data of Tibetan Mastiffs,indigenous dogs,bread dogs and wolves.SNPs on 38 autosomes genome of 10 Tibetan Mastiffs,10 Yingjiang indigenous dogs and 2 Tibetan wolves showed that there is an extremely significant gene flow between Tibetan grey wolf and Tibetan Mastiff and its ratio is 11%.The results of PCAdmix also showed that 0.62-0.89%genetic region of Tibetan Mastiff population comes from Tibetan grey wolf.Furthermore,two regions shared at least 14 out of 20 haplotypes(P=0.011)locating on chromosome 10(48,563,580-48,679,855)and chromosome 21(28,069,514-28,119,769),respectively.The region on chromosome 10 shared 71.1 kb with the EPAS1 gene,which is 85.38%of the length of EPAS1 gene.We find two nonsynonymous mutations related to adaptability to highland in the region of chromosome 21.Three hypotheses had proposed to account for the region on chromosome 10 of Tibetan Mastiffs from Tibetan grey wolf:introgression from Tibetan grey wolf,incomplete lineage sort or convergent evolution.We calculate the theoretical length in the region according to known recombination ratio and divergence time between wolf and dog,and found that the actual length(116.3 kb)is 16 times than the theoretical length(7.2kb).Therefore,the hypothesis of incomplete lineage sorting might be rejected because it is impossible to be so long due to recombination since divergence between dog and wolf.We then used SNPs of coding region and no-coding region to construct phylogenetic trees,respectively.The two resulting phylogenetic trees were concordant with each other.We simulated the selective sites under 4 categories of different selective intensions(200,500,1000 and 2000)and 2 categories of initial derived allele frequency(0.01 and 0.05),and found that the theoretical values were much less than observed value.It is suggested the possibility of convergent evolution could be negated.The result of haplotype pattern also shows Tibetan Mastiff and Tibetan grey wolf show more similar pattern to each other than Yingjiang indigenous dog.Overall,it is illustrated that EPAS1 of Tibetan Mastiff maybe had been introgressed from the Tibetan grey wolf.