The 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. We 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. Our 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.

Through long term natural and artificial selection, domestic sheep (Ovis aries) have become adapted to a diverse range of agro-ecological environments and display multiple phenotypic traits. Characterization of diversity and selection signature is essential for genetic improvement, understanding of environmental adaptation, as well as utilization and conservation of sheep genetic resources. Here, we aimed to assess genomic diversity, population structure, and genomic selection among five Chinese native sheep breeds using 600K high density SNP genotypes. A total of 96 animals of the five breeds were selected from different geographical locations with extremely dry or humid conditions. We found a high proportion of informative SNPs, ranging from 93.3% in Yabuyi to 95.5% in Wadi, Hu, and Hetian sheep. The average pairwise population differentiation (F_ST) between the breeds was 0.048%, ranging from 0.022% to 0.054%, indicating their low to moderate differentiation. PCA, ADMIXTURE, and phylogenetic tree analyses revealed a clustering pattern of the five Chinese sheep breeds according to their geographical distribution, tail type, coat color, body size, and breeding history. The genomic regions under putative selection identified by F_ST and XP-EHH approaches frequently overlapped across the breeds, and spanned genes associated with adaptation to extremely dry or humid environments, innate and adaptive immune responses, and growth, wool, milk, and reproduction traits. The present study offers novel insight into genomic adaptation to dry and humid climates in sheep among other domestic animals and provides a valuable resource for further investigation. Moreover, it contributes useful information to sustainable utilization and conservation of sheep genetic resources.

The identification of genome-wide selection signatures can provide insights on the mechanisms of natural and/or artificial selection and uncover genes related to biological functions and/or phenotypes. Tibetan sheep are an important livestock in Tibet, providing meat and wool for Tibetans who are renown for breeding livestock that adapt well to high altitudes. Using whole-genome sequences with an effective sequencing depth of 5×, we investigated the genomic diversity and structure and, identified selection signatures of White Tibetan, Oula and Poll Dorset sheep. We obtained 30,163,679 Single Nucleotide Polymorphisms (SNPs) and 5,388,372 indels benchmarked against the ovine Oar_v4.0 genome assembly. Next, using F_ST, ZHp and XP-EHH approaches, we identified selection signatures spanning a set of candidate genes, including HIF1A, CAPN3, PRKAA1, RXFP2, TRHR and HOXA10 that are associated with pathways and GO categories putatively related to hypoxia responses, meat traits and disease resistance. Candidate genes and GO terms associated with coat color were also identified. Finally, quantification of blood physiological parameters, revealed higher levels of mean corpuscular hemoglobin measurement and mean corpuscular hemoglobin concentration in Tibetan sheep compared with Poll Dorset, suggesting a greater oxygen-carrying capacity in the Tibetan sheep and thus better adaptation to high-altitude hypoxia. In conclusion, this study provides a greater understanding of genome diversity and variations associated with adaptive and production traits in sheep.

MicroRNAs (miRNAs) are evolutionarily conserved, small, non-coding RNAs that have emerged as key regulators of myogenesis. Here, we examined the miRNA expression profiles of developing sheep skeletal muscle using a deep sequencing approach. We detected 2,396 miRNAs in the sheep skeletal muscle tissues. Of these, miR-192 was found to be up-regulated in prenatal skeletal muscle, but was down-regulated postnatally. MiR-192 expression also decreased during the myogenic differentiation of sheep satellite cells (SCs). MiR-192 overexpression significantly attenuated SCs myogenic differentiation but promoted SCs proliferation, whereas miR-192 inhibition enhanced SCs differentiation but suppressed SCs proliferation. We found that miR-192 targeted retinoblastoma 1 (RB1), a known regulator of myogenesis. Furthermore, knockdown of RB1 in cultured cells significantly inhibited SCs myogenic differentiation but accelerated SCs proliferation, confirming the role of RB1 in myogenesis. Taken together, our findings enrich the ovine miRNA database and outline the miRNA transcriptome of sheep during skeletal muscle development. Moreover, we show that miR-192 affects SCs proliferation and myogenic differentiation via down-regulation of RB1.

Cashmere goats are valuable genetic resources which are famous worldwide for their high-quality fiber. Runs of homozygosity (ROHs) have been identified as an efficient tool to assess inbreeding level and identify related genes under selection. However, there is limited research on ROHs in cashmere goats. Therefore, we investigated the ROH pattern, assessed genomic inbreeding levels and examined the candidate genes associated with the cashmere trait using whole-genome resequencing data from 123 goats. Herein, the Inner Mongolia cashmere goat presented the lowest inbreeding coefficient of 0.0263. In total, we identified 57,224 ROHs. Seventy-four ROH islands containing 50 genes were detected. Certain identified genes were related to meat, fiber and milk production (FGF1, PTPRM, RERE, GRID2, RARA); fertility (BIRC6, ECE2, CDH23, PAK1); disease or cold resistance and adaptability (PDCD1LG2, SVIL, PRDM16, RFX4, SH3BP2); and body size and growth (TMEM63C, SYN3, SDC1, STRBP, SMG6). 135 consensus ROHs were identified, and we found candidate genes (FGF5, DVL3, NRAS, KIT) were associated with fiber length or color. These findings enhance our comprehension of inbreeding levels in cashmere goats and the genetic foundations of traits influenced by selective breeding. This research contributes significantly to the future breeding, reservation and use of cashmere goats and other goat breeds.

Homozygosity of long sequence genotypes are a result of parents transmitting identical haplotypes, which can be used to estimate their auto-zygosity. Therefore, we used high-density SNP Chip data to characterize the auto-zygosity of each breed according to the occurrence and distribution of runs of homozygosity (ROH). Subsequently, we identified the genomic regions with high runs of homozygosity frequencies within individuals of each breed. We selected 96 sheep samples from five local Chinese sheep breeds belonging to different geographical locations. We identified 3046 ROHs within the study breed individuals, among which the longer segments (>1–5 Mb) were dominant. On average, ROH segments covered about 12% of the genomes; the coverage rate of OAR20 was the lowest and that of OAR2 was the highest. The distribution analysis of runs of homozygosity showed that the detected ROH mainly distributed between >26 and 28 Mb. The Hetian and Hu sheep showed the lowest ROH distribution. The estimation of homozygosity level reflects the history of modern and ancient inbreeding, which may affect the genomes of Chinese indigenous sheep breeds and indicate that some animals have experienced recent self-pollination events (Yabuyi, Karakul and Wadi). In these sheep breeds, the genomic regions were assumed to be under selection signatures frequently in line with long ROH. These regions included candidate genes associated with disease resistance traits (5S_rRNA), the innate and adaptive immune response (HERC2 and CYFIP1), digestion and metabolism (CENPJ), growth (SPP1), body size and developments (GJB2 and GJA3). This study highlighted new insights into the ROH patterns and provides a basis for future breeding and conservation strategies of Chinese sheep breeds.