BackgroundThe Tibetan cashmere goat (Capra hircus), one of the most ancient breeds in China, has historically been a critical source of meat and cashmere production for local farmers. To adapt to the high-altitude area, extremely harsh climate, and hypoxic environment that the Tibetan cashmere goat lives in, this goat has developed distinct phenotypic traits compared to lowland breeds. However, the genetic components underlying this phenotypic adaptation remain largely unknown.ResultsWe obtained 118,700 autosomal SNPs through exome sequencing of 330 cashmere goats located at a wide geographic range, including the Tibetan Plateau and low-altitude regions in China. The great majority of SNPs showed low genetic differentiation among populations; however, approximately 2-3 % of the loci showed more genetic differentiation than expected under a selectively neutral model. Together with a combined analysis of high- and low-altitude breeds, we revealed 339 genes potentially under high-altitude selection. Genes associated with cardiovascular system development were significantly enriched in our study. Among these genes, the most evident one was endothelial PAS domain protein 1 (EPAS1), which has been previously reported to be involved in complex oxygen sensing and significantly associated with high-altitude adaptation of human, dog, and grey wolf. The missense mutation Q579L that we identified in EPAS1, which occurs next to the Hypoxia-Inducible Factor-1 (HIF-1) domain, was exclusively enriched in the high-altitude populations.ConclusionsOur study provides insights concerning the population variation in six different cashmere goat populations in China. The variants in cardiovascular system-related genes may explain the observed phenotypic adaptation of the Tibetan cashmere goat.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2449-0) contains supplementary material, which is available to authorized users.

Copy number variants (CNVs) represent a form of genomic structural variation underlying phenotypic diversity. In this study, we used the Illumina Ovine SNP 600 K BeadChip array for genome-wide detection of CNVs in 48 Chinese Tan sheep. A total of 1,296 CNV regions (CNVRs), ranging from 1.2 kb to 2.3 Mb in length, were detected, representing approximately 4.7% of the entire ovine genome (Oar_v3.1). We combined our findings with five existing CNVR reports to generate a composite genome-wide dataset of 4,321 CNVRs, which revealed 556 (43%) novel CNVRs. Subsequently, ten novel CNVRs were randomly chosen for further quantitative real-time PCR (qPCR) confirmation, and eight were successfully validated. Gene functional enrichment revealed that these CNVRs cluster into Gene Ontology (GO) categories of homeobox and embryonic skeletal system morphogenesis. One CNVR overlapping with the homeobox transcription factor DLX3 and previously shown to be associated with curly hair in sheep was identified as the candidate CNV for the special curly fleece phenotype in Tan sheep. We constructed a Chinese indigenous sheep genomic CNV map based on the Illumina Ovine SNP 600 K BeadChip array, providing an important addition to published sheep CNVs, which will be helpful for future investigations of the genomic structural variations underlying traits of interest in sheep.

High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski’s horses added for comparison. We find that Tibetan horses do not descend from Przewalski’s horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages.

Detection of selection footprints provides insight into the evolution process and the underlying mechanisms controlling the phenotypic diversity of traits that have been exposed to selection. Selection focused on certain characters, mapping certain genomic regions often shows a loss of genetic diversity with an increased level of homozygosity. Therefore, the runs of homozygosity (ROHs), homozygosity by descent (HBD), and effective population size (Ne) are effective tools for exploring the genetic diversity, understanding the demographic history, foretelling the signature of directional selection, and improving the breeding strategies to use and conserve genetic resources. We characterized the ROH, HBD, Ne, and signature of selection of six Chinese goat populations using single nucleotide polymorphism (SNP) 50K Illumina beadchips. Our results show an inverse relationship between the length and frequency of ROH. A long ROH length, higher level of inbreeding, long HBD segment, and smaller Ne in Guangfeng (GF) goats suggested intensive selection pressure and recent inbreeding in this breed. We identified six reproduction-related genes within the genomic regions with a high ROH frequency, of which two genes overlapped with a putative selection signature. The estimated pair-wise genetic differentiation (FST) among the populations is 9.60% and the inter- and intra-population molecular variations are 9.68% and 89.6%, respectively, indicating low to moderate genetic differentiation. Our selection signatures analysis revealed 54 loci harboring 86 putative candidate genes, with a strong signature of selection. Further analysis showed that several candidate genes, including MARF1, SYCP2, TMEM200C, SF1, ADCY1, and BMP5, are involved in goat fecundity. We identified 11 candidate genes by using cross-population extended haplotype homozygosity (XP-EHH) estimates, of which MARF1 and SF1 are under strong positive selection, as they are differentiated in high and low reproduction groups according to the three approaches used. Gene ontology enrichment analysis revealed that different biological pathways could be involved in the variation of fecundity in female goats. This study provides a new insight into the ROHs patterns for maintenance of within breed diversity and suggests a role of positive selection for genetic variation influencing fecundity in Chinese goat.

Body size, one of the most important quantitative traits under evolutionary scrutiny, varies considerably among species and among populations within species. Revealing the genetic basis underlying this variation is very important, particularly in humans where there is a close relationship with diseases and in domestic animals as the selective patterns are associated with improvements in production traits. The Debao pony is a horse breed with small body size that is unique to China; however, it is unknown whether the size-related candidate genes identified in Western breeds also account for the small body size of the Debao pony. Here, we compared individual horses from the Debao population with other two Chinese horse populations using single nucleotide polymorphisms (SNPs) identified with the Equine SNP 65 Bead Chip. The previously reported size-related candidate gene HMGA2 showed a significant signature for selection, consistent with its role observed in human populations. More interestingly, we found a candidate gene TBX3, which had not been observed in previous studies on horse body size that displayed the highest differentiation and most significant association, and thus likely is the dominating factor for the small stature of the Debao pony. Further comparison between the Debao pony and other breeds of horses from around the world demonstrated that TBX3 was selected independently in the Debao pony, suggesting that there were multiple origins of small stature in the horse.