Genome-wide Detection Of Selection Signatures Reveals Selective Imprints Of Chinese Indigenous Sheep Breeds During Domestication

Sheep were one of the earliest domesticated animals in the world and one of the most successful domesticated animals in the Neolithic age.During this process,strong artificial and natural selection caused remarkable changes in the behavioral,physiological,and morphological phenotype.After that,the domesticated sheep spread to every corner of the world along with the migration of human activities,forming different breeds or groups with different traits,such as fecundity,environmental adaptability,etc.However,the genetic mechanisms underlying these phenotypic variation and domestication in natural and artificial selection are still not clear.China has a long history of sheep breeding and rich genetic resources.It is an ideal genetic resource for studying genetic mechanism of sheep domestication mode and variety differentiation.In this study,we analyzed variation patterns and selective regions in Chinese domestic sheep by whole-genome resequencing of 338 sheep from five representative indigenous Chinese breeds(Altay,Duolang,Hu,Mongolian and Tibetan sheep)and compared the data with the genomes of their wild ancestors(Asian mouflon,Ovis orientalis).The main findings are as follows:(1)Genotyping of 10 pooled genomes(2 pools per breed)of five indigenous Chinese sheep breeds(Tibetan sheep,Mongolian sheep,Altay sheep,Hu sheep,and Duolang sheep)by comparison of with publicly available genomes of 17 Asiatic wild sheep(Asiatic mouflon)yielded a total of 1,427 Gb of raw genome data.Stringent quality filtering resulted in a yield of 1,172 Gb of genome clean data for the subsequent analyses.(2)A total of 64,105,124 SNP and 7,985,424 In Del were detected from these five Chinese native sheep breeds and Asiatic mouflon.We found higher genomic diversity in the wild sheep than in the five indigenous Chinese sheep breeds,this was reflected by the higher rate of SNP heterozygosity and number of In Del in the wild sheep,which indicates that the Chinese native sheep breeds have undergone intense environmental and artificial selection.(3)We integrated these five native Chinese sheep breeds as a whole(domestic sheep)and calculated pooled homozygosity(HP)and fixation index(FST)in the 150-kb windows with 75-kb sliding steps along the sheep genome.101 putative selective regions weredetected in 26 autosomes and the X chromosome.Gene ontology analysis revealed significant enrichment of the 365 protein-coding genes embedded in the selective regions in many biology processes,including biological regulation,cellular process and immune response,which were associated with reproduction,neurodevelopment,bone development,digestive tract development and vision.(4)Homozygosity(HP)and fixation index(FST)analyses were also performed in the five native Chinese sheep breeds,respectively.For Altay sheep,95 putative selective regions(total length,21.375 Mb;0.827% of the complete genome)were detected from the 26 autosomes and Chr X.For Duolang sheep,99 putative selective regions(total length,20.775 Mb;0.804% of the complete genome)were detected from the 26 autosomes and Chr X.For Hu sheep,100 putative selective regions(total length,22.20Mb;0.859% of the complete genome)were detected from the 26 autosomes and Chr X.For Mongolian sheep,100 putative selective regions(total length,22.875 Mb;0.885% of the complete genome)were detected from the 26 autosomes and Chr X.For Tibetan sheep,104 putative selective regions(total length,22.575 Mb;0.873% of the complete genome)were detected from the 26 autosomes and Chr X.Among these potential selective regions,20 putative selective regions(total length,3.75 Mb;1.451% of the complete genome)were identified sharing by all these five native Chinese sheep breeds,18 of which were located on autosomes and the other 2 were located on Chr X.Gene ontology analysis revealed significant enrichment of the 67 candidate genes embedded in this 20 selective regions in 180 GO terms,including bone morphogenesis,fibroblast growth factor receptor apoptotic signaling pathway,negative regulation of developmental growth,embryonic development,and neural crest cell development.(5)Four genes in the three shared selected regions of all five native Chinese sheep breeds,phosphodiesterase 6B(PDE6B),pantothenate kinase 2(PANK2),forkhead box C1(FOXC1)and GDP-mannose 4,6-dehydratase(GDMS),were enriched for HPO(human phenotype ontology)categories associated with eye development and maintenance as well as vision.The c.G2994C/p.A982 P mutation located in the PDE6 B protein HDc domain is almost fixed in all five domestic sheep breeds,but not in the wild breed,which may resultfrom the selective pressure at the early stage of sheep domestication,suggesting the potential contribution of the mutation of PDE6 B in the evolution of vision in domestic sheep.These results suggest that variations in the GAF and HDc domains of PDE6 B have played important roles in the evolution of vision in domestic sheep.(6)Only two unique regions passed the threshold described previously for the autosomes.One of these regions harbored the androgen receptor(AR)gene and the other harbored the oligophrenin 1(OPHN1)gene.The c.A1579G/p.I579 V mutation located in the OPHN1 protein Rho GAP domain is almost fixed in all five domestic sheep breeds.It can be speculated that the mutations of AR and OPHN1 gene is associated with the reproductive behavior and temperament changes in the early stage of sheep domestication.(7)Some specific selective genes that reflect the characteristics of each breed were also identified in the five native Chinese sheep breeds.These included two novel genes related to hypoxia adaptability(CYP17)in Tibetan sheep and heat tolerance(DNAJB5)in Duolang sheep,and some known genes associated with litter size(BMPR-IB)in Hu sheep,the presence or absence of horns(RXFP2)in Hu and Duolang sheep,vertebral number variations(Hox A gene cluster)in Mongolian sheep,the short-tailed phenotype(T,c.G334T/p.G112W)in Altay and Duolang sheep,and the ear size(MSRB3)in Duolang sheep.In this study,we performed high coverage genome sequencing of five representative native Chinese sheep breeds and compared these data with publicly available genome sequences of 17 wild sheep.We constructed high quality genetic variation map of five native sheep breeds.Common and specifically selected regions and genes that reflect the characteristics of each native sheep breed were identified by selective signal analysis.We also found some genes and variations related to important physiology phenotypes and economic traits,which play important roles in domestication and variety differentiation,such as vision,neurodevelopment,reproduction and adaptability.These results preliminarily revealed the selection model of Chinese native sheep domestication.