Population-scale Structural Variation And Domestication

The domestic yak(Bos grunniens)is a species of long-haired domesticated cattle belonging to the Bos genus,generally considered to be a descendant of the wild yak(Bos mutus),which plays an important role in the lives of nomadic herders on the Qinghai-Tibetan plateau and is essential for survival and living at high altitudes of Tibetan.Previous population genetic studies found that domestic yaks were domesticated about 7,100 years ago,genes related to the nervous system were under selection during domestication.In this study,two main results were accomplished.First,we assembled: we reported a chromosomal-level reference genome sequence for domestic yak,which is also the highest quality reference genome of all ruminants to date.Second,we identified genomic structural variation in domestic and wild yak populations using population-level long-read whole genome sequencing and presented,representing the first yak structural variation map.We further explored the The relationship between genomic structural variations and yak domestication as well.The main findings are summarized as follows.1)The genome of domestic yak was sequenced at high depth using three different library-building sequencing methods,i.e.,Nanopore,Illumina and Hi-C.After sequencing,the genome was assembled firstly using Nanopore sequences,followed by genome error correction using Illumina.The obtained data,which resulted a genome size of 2.83 Gb with contig N50 of 44.72 Mb.The contigs were further mounted and localized to all 31 chromosomes.The length of scaffold N50 was 114.39 Mb after final using of Hi-C reads.Our assembled genome upgraded the reference genome of the domestic yak from scaffold level to chromosome level.2)Prediction of repetitive elements,non-coding elements and protein-coding genes was carried out using various methods and tools.The results showed that 43.90%of this newly assembled genome is composed of repetitive sequences,and about 0.72%of the genome encodes multiple non-coding RNAs.A total of 21,232 protein-coding genes were predicted,similar to the results of the genome assembled using Illumina sequences.Functional annotation of the protein-coding genes showed that 97% of the coding genes have corresponding functions.3)Gene family analysis of the newly assembled domestic yak genome and genomes of other related species showed that all genes in the yak genome could be clustered into 15,662 gene families.Phylogenetic analyses of the single-copy genes suggested that wild and domestic yaks were sister to each other,which were together related to bison and wison,but distantly related to other Bos species.The result showed that domestic and wild yaks form sister clades in the phylogenetic tree,and they are phylogenetically closer to American bison(Bison bison)and wisent(Bison bonasus)of Bison genus than species of Bos genus.4)We used three different methods to construct structural variant maps between domestic and wild yaks,resulting in 372,903,125,531 and 353,307 structural variants based on long read length,short read length and genome assembly,respectively.We further used three-generation whole genome sequencing to identify structural variants,we performed genetic analysis between 23 domestic yaks and 6 wild yaks using the third-generation whole genome sequencing data.Annotation of the SVs indictated that the majority of SVs comprised of repetitive elements,and repetitive elements varies by different length of SVs.5)By assessing structural variants that were highly differentiated between populations,we obtained 3,680 structural variants that may have been subject to selection during domestication,which involve 725 protein-coding gene regions.Functional enrichments of the genes revealed that they are mainly associated with phenotypes of domestication syndromes such as neurological development and psychiatric diseases.Some genes were also associated with economic traits of domesticated animals,such as immunity,fat storage and reproduction.In summary,from the perspective of genetic resources,this study assembles a high-quality reference genome for a domestic yak and reports the first genomic structural variation map of both wild and domest yaks.These results provide valuable genetic resources and materials for subsequent studies of yaks.We further reveal the relationship between genomic structural variation and yak domestication.In addition,we provide an integrated approach to mine structural variations in non-model organisms,and offers a new perspective on genetic mechanisms of animal domestication.