| The now-extinct wild aurochs,Bos primigenius（B.primigenius）,may have originated from India and are estimated to have evolved there between 1.5 and 2 million years ago.During the Pleistocene era,the wild aurochs spread to other parts of Asia,to northern Africa,and to Europe.Domesticated extant cattle can be categorized into two major geographic taxa:humpless taurine（B.taurus in Europe,Africa,and Asia）and humped indicine（B.indicus in South Asia,and East Africa）,which diverged from each other 1,000,000-250,000 years ago.According to previous reports,B.taurus was domesticated 10,500 years before the present（BP）in the Near East,while B.indicus was domesticated approximately 8,500 years BP in southern Asia,with the emergence of agriculture-based civilization.These breeds are representative of ruminants that served as important sources of hides,meat and milk for human needs and as draught animals for pulling carts,plowing and performing other tasks in less mechanized cultures8.Benefiting from artificial selection,more than 800 cattle breeds were established throughout the world;of them,53 breeds with different intrinsic characteristics originated from and are endemic in China,which are important genetic resources for worldwide cattle.Chinese cattle have long been used as draught animals,enhancing their pronounced merits in parasite resistance,utilization of roughage-based diets and tolerance to environmental challenges.Chinese cattle breeds are roughly divided into 3 groups according to different ecological characteristics and sex chromosome polymorphisms:the southern group,the central group and the northern group.Cattle in the north and northeast are primarily of B.taurus ancestry.Cattle in southern China are predominantly B.indicus.Cattle located between these two geographical regions are B.taurus×B.indicusadmixture.The origin and phylogenetic relationships of Chinese cattle are very complicated,and the origin of Chinese indicine cattle is controversial.Furthermore,the genetic basis of adaptive evolution is not clear.Recently,whole-genome sequencing of representative individuals from diverse populations has become feasible;previous genomic studies were primarily focused on the characteristics of European breeds used for beef and milk production,such as Hereford,Fleckvieh,Black Angus,Jersey,and Limousin.Notably,genomic studies of Chinese cattle remain limited,especially regarding haplotype dissection,population structure,and demographic and breeding histories.In this study,we performed whole-genome sequencing on six phenotypically and geographically diverse domestic Chinese cattle breeds and on two non-Chinese cattle breeds.We also integrated the publicly available whole-genome sequence data,which includes 7 breeds.The objectives were to construct the haplotypes,to infer the phylogeny and population stratification.Integrating the available sequence data on cattle with our own data,we remodeled the world cattle Demography,identified differences among indicine cattle from China and South Asia,and detected genes and corresponding variants that are associated with agriculturally important traits.Our analyses provide new insights into the origins and local breeding of Chinese cattle and their relationship to worldwide domestic breeds.（1）Whole-genome sequencing of 75 samples generated a total of 27.52 billion paired-end reads accomplished an average depth of 11.4-fold and an average coverage of98.46%.We integrated other published data（15 samples from 3 indicine breeds and 61 from 4taurine breeds）.We detected a total of 57.22 million single-nucleotide polymorphisms（SNPs）and 5.27 million small insertions and deletions（InDels）.More than half（59.90%and 72.45%）of the SNPs and InDels were absent in the SNP Database（dbSNP,release 140）;the novel variants,which substantially expanded the set of genetic variants in cattle,were mainly contributed by B.indicus and Chinese breeds,especially by LQC and QCC.The rare variants capture 37.64%in the data set,approximately 21.54 million autosomal variants had a<1%frequency,approximately 16.38 million had frequencies between 1%and 5%,and approximately 19.30 million only had a>5%frequency.Chinese cattle had high genetic diversity.（2）Comparing the genome sequencing data of Chinese cattle to those from various cattle breeds revealed the geographically distinct demographic histories of Chinese cattle.Structure results（K=2）showed that LQC and other indicine cattle breeds belong to the indicine lineage（Fig.1c）.The PCA,phylogenetic tree,FST and SNPs analysis distinctly showed that LQC did not cluster to other indicine cattle,indicating that LQC and indicine cattle from South Asia vary in genetic background.Therefore,we propose that South China may be one of the independent origin sites of indicine cattle.（3）Furthermore,we determined the relationships between four indicine breeds and non-indicine breeds using Dstatistics and found that Chinese cattle shared significantly more alleles with LQC than with other typical indicine breeds.We used the D4PP test and found that the ancestors of LQC were separated directly and early from the ancestors of B.indicus and B.taurus.The maximum-likelihood phylogeny estimated that the divergence between the ancestors of LQC and the ancestors of cattle（B.indicus and B.taurus）occurred approximately 2-1.3 million years ago.The uplift of the Tibetan plateau and the Yuanmu movement（approximately 1.6 million years ago）helped create the higher mountains of the Himalayas and led to the split between the northern and the Himalayan snub-nosed monkey species.（4）We also discovered many potential domestic sweeps related to breed-specific characteristics,such as SPTBN5 gene associated with the immune system in Qinchuan cattle（QCC）,resulting from indicine introgression;BBS2 and LTA4Hinvolved in fat synthesis in JBC;and RCAN1,CACNB4 and RHOA contributing to fetal weight and perinatal lethality in RAN.Whole-genome sequencing of the representative Chinese cattle breeds and other breeds（JBC and RAN）generated a comprehensive catalog of genetic variations.Our results suggest that South China was one of the independent origin centers of indicine cattle that separated early from the ancestors of Bos indicus and Bos taurus cattle.Moreover,the indicine descent of Chinese cattle might have originated from Leiqiong cattle（LQC）or LQC-like indicine cattle from South China.These findings substantially expand the catalog of genetic variants in cattle and reveal new insights into the evolutionary history and domestication traits of Chinese cattle.Our study also exhibits the clear signatures of select genes with phenotypic traits in Chinese cattle,which will be useful in the cattle breeding. |
