Genome-wide Genetic Variation And High Altitude Adaptation Of Gene Expression In Yak

The yak (Bos grunniens) is one of the few animals that can thrive in the harsh environment of the Qinghai-Tibetan Plateau and adjacent alpine regions. For thousands of years, yak provided essential resources allowing Tibetans to live at high altitudes and also became an important part of Tibetan culture. However, the progress of long-term pure breeding has resulted in severe traits degradation in domestic yaks, including meat quality and disease resistance, which had significant impact on the stability of farming and husbandry production in the Qinghai-Tibetan Plateau and surrounding regions. Thus, it is essential to protect and utilize the excellent germplasm and genetic resources of yak, which will provide us important basis for yak genetic improvement. In addition, as the most successful high-altitude adapted mammal in the world, yak can overcome major environmental challenges (hypoxia, cold and scarcity of food), making yak an ideal system for studying high altitude adaptation. In the present study, we aimed to investigate two significant scientific issues of yak:(1) construct the genome-wide variation map for both domestic and wild yak to provide essential genetic resources for maker-assisted breeding and for the study of genetic diversity in both yak and other bovid species; (2) reveal the molecular mechanism of high-altitude adaptation of yak through comparative transcriptome analysis.(1) Genome-wide variation map in yakAlthough there are 12 local varieties of yak in China, little significant difference was detected between varieties and most of them have been severely degraded in a pure breeding way. Meanwhile, wild yak, the direct ancestor of domestic yak, is still alive at present and can provide important genetic resource for the improved varieties. However, genetic variation within and between wild and domestic yak remain limited. Here, we applied the latest strategy to re-assemble the genome sequence of yak, in which both the continuity and accuracy were enhanced and the N50 of the genome sequence was prolonged from 1.5M to 2.6M. Based on the updated genome, we re-sequenced three wild and three domestic yaks respectively, with an average of 5-fold depth using our published domestic yak genome as a reference. More than 95% of the genome regions were covered by each individual. A total of 8.38 million SNPs (of 7.14 million SNPs was firstly discovered),383,241 InDels and 126,352 structural variants were identified between the six yaks. We observed a modest genetic divergence between domestic and wild yak and most of the variation was shared between these two groups, which indicate a preliminary domestication of yak. We further identified Potential Selected Regions (PSRs) for domestic yak and the genes in PSRs are correlated with disease resistance and nervous system. These genonic resources are illustrated in the Yak Genome Database (http://me.lzu.edu.cn/yak) and can be further used on genetic diversity research and superior breeds selection of yak and other bovid species.(2) High altitude adaptation of gene expressionDNA sequence variation has been widely reported as the genetic basis for adaptation, in both humans and other animals, to the hypoxic environment experienced at high altitudes. However, little is known about the patterns of gene expression underlying such hypoxic adaptations. In this study, we examined differences in the transcriptomes of four organs (heart, kidney, liver and lung) between yak and cattle, two closely related species distributed at high and low altitudes, respectively. Our comparative transcriptome analyses of four organs in cattle and yak revealed that:(i) of the four organs examined, heart and lung shows the greatest differentiation between the two species in terms of gene expression profiles and the DEGs show enrichment in heart-associated GO terms and KEGG pathways (GO:0055117, regulation of cardiac muscle contraction; GO:0050793, calcium ion binding; hematopoietic cell lineage, ko04640); meanwhile, both neural regulation and humoral regulation were participated in the enhancement of cardiac contractility in yak to provide sufficient oxygen in hypoxia environment; (ⅱ) the DEGs associated with inhibiting the proliferation of vascular smooth muscle (BMPR2) and L-glutamate import (HIT, SLC1A1, SLC1A2) probably play important roles for yak to avoid hypoxia related disease such as hypoxia pulmonary vasoconstriction and excitotoxicity; (ⅲ) the co-evolution of protein sequences and gene expression patterns in genes associated with material metabolism (ko03010, ribosome pathway) and energy metabolism (ko00190, oxidative phosphorylation pathway) are likely to be correlated with the optimization of the yak metabolic system to resist hypoxia.