Accumulation Of Deleterious Mutations In The Yak Genome

The yak(Bos grunniens)is a large domestic animal,which is living in the Qinghai-Tibet plateau(QTP)and the extreme harshness environments.Around 7,300 years ago,human began to domesticate the yaks,and the domestic yaks provided the basic resources(food,shelter,fuel and transport)that are necessary for Tibetans.Following the domestication,a further increased in the effective population size of domestic yaks later and it also provided a foundation for agricultural development.The ancestral wild yak population still exists with domestic populations,which makes the yaks become a model species for studying the accumulation of deleterious mutations.Deleterious mutations play an important functional role in affecting trait phenotypes in ways that decrease the fitness of organisms.Therefore,estimating the frequency of occurrence and the abundance of deleterious mutations has been a topic of much interest,especially in cultivated crops and domesticated livestock.The processes of domestication and breeding allow deleterious mutations to persist at high frequency and identifying deleterious mutations is particularly important for breed improvement.Based on the draft genome sequence of the yak and the study of yak whole-genome resequencing reveals domestication signatures and prehistoric population expansion,we identified the deleterious mutations by three software,and inferred the effects of the deleterious genes on the domestic yak populations.Here,we assessed genome-wide patterns of deleterious variation in 59 domestic and 13 wild yaks using genome resequencing data.Based on the intersection of results given by three methods(PROVEAN,PolyPhen2 and SIFT4G),we identified 3,187 putative deleterious mutations affecting a total of 2,586 genes in domestic yaks,and 2,067 deleterious mutations in 1,701 genes in wild yaks.Multiple lines of evidence indicate a significant increase in the load of deleterious mutations in the domesticated yak compared with wild yaks.Domestic yaks have more private deleterious mutations than wild yaks.And domestic yaks owned more coding sequence region sites near sweeps.Further,the results proved that the domestic yaks accumulated more variation sites during the artificial selection.We evaluated the function of private deleterious genes of the domestic yak,found that private deleterious genes in domestic yaks were enriched mainly in perception of sensory perception and response to stimulus.However,we did not get any significant enrichment in the wild yak.In addition,we corresponded 837 private deleterious genes in yaks into the Mendelian genetic diseases database,and identified 36 genes related to genetic disease,including 8 genes involved in diseases of sensory perception,3 genes affecting skeletal development,and 8 genes related to immune response and DNA repair systems,and some genes influencing processes in the developing nervous system.We present the first study in identification of deleterious mutations in yak genome and in analyses of comprehensive comparative relationship in these deleterious mutations among different yak populations so far.This study not only adds the understanding in the genetic basis of yak domestication,but also provides a rich catalog of variants which will facilitate future breeding-related researches on yak and other bovine species.