Genome Sequence And Adaptive Evolution Of The Yak

The Qinghai-Tibetan Plateau is characterized by its high altitude and very low annual average temperature. Yak (Bos grunniens) grows on this plateau at altitudes from 3000 to 5500 m with a well adaptation to the cold and hypoxia environments. In this study, we firstly presented a high-quality draft genome sequence of one domestic yak using next-generation sequencing technology. We then analyzed the adaptive evolution of the yak through comparing its genome sequences with those of the cattle growing in the low altitude.We assembled the draft genome of the yak with N50 sequence contigs reaching 20 kb and N50 scaffolds reaching 1.5Mb. The total length of the scaffolds is around 2.66 Gb, close to the 2.73 Gb, the genome size of the cattle. The total sequencing depth was 65 x and more than 98% of the nucleotides had been sequenced more than 20×. Through further assessments by sequencing Fosmids and transcriptsome, the assembled scaffolds were found to have covered more than 90% and 95% of the euchromatic regions and genic regions, respectively. We identified more than 3.7 million heterozygous single nucleotide polymorphisms in this diploid yak genome, which is about 2.5 times higher than that from the cattle genome. We predicted 22,282 protein-coding genes, with a core set of 13,810 genes orthologous with the major sequenced mammalian species. These predicted genes have an average transcript length of 29,107 bp, coding length of 1,475 bp, and a mean of eight exons per gene, all similar to those observed for cattle and human. A total of 97.5% of the genes matched at least with one of the public protein databases. We further evaluated the predicted coding sequences by using mRNA-seq data from heart, liver, lung, stomach, brain, spleen, muscle and ovary. We found that 71% of the predicted genes were represented in the transcriptome dataset.In the yak, we identified 8,923 genes, which are high orthologous to those from cattle, horse, mouse, chimpanzee and human. Based on the evolutionary analyses of these orthologs, we found that Ks was significantly lower in the yak than in the cattle lineage, indicating an obvious difference in neutral evolution rates between these two lineages. This trend was also obvious when the divergence at the fourfold-degenerate sites was compared. However, the yak lineage had a significantly higher overallω(Ka/Ks) than the cattle lineage, suggesting that the yak may have accumulated more amino acid substitutions than the cattle due to the adaptive evolution under the arid habitat. We also analyzed adaptive evolution of the genes, which were significantly enriched for a large number of functional categories according to the Gene Ontology database. We found that those genes related to mitochondrial oxidative phosphorylation (OXPHOS) and hypoxia between yak and cattle showed greatest differences than the others. We then compared the number of positively selected genes (PSGs) classified as’oxidative phosphorylation’ and ’response to hypoxia’ along the cattle and yak lineage, and found that the number of PSGs is significantly higher in the yak than in the cattle. All these lines of evidence suggest that genes related to energy metabolism and hypoxia-response pathways may have played an important role in the adaptation history of the yak to the arid habitat and therefore experienced a higher adaptive evolution than the other genes.