High-altitude stress threatens the survival rate of Tibetan sheep and reduces their fertility. However, the molecular basis of this phenomenon remains elusive. Here, we used RNA-seq to elucidate the transcriptome dynamics of high-altitude stress in Tibetan sheep ovaries. In total, 104 genes were characterized as high-altitude stress-related differentially expressed genes (DEGs). In addition, 36 DEGs contributed to ovarian follicle development, and 28 of them were downregulated under high-altitude stress. In particular, high-altitude stress significantly suppressed the expression of two ovarian lymphatic system marker genes: LYVE1 and ADAMTS-1. Network analysis revealed that luteinizing hormone (LH)/follicle-stimulating hormone (FSH) signaling-related genes, such as EGR1, FKBP5, DUSP1, and FOS, were central regulators in the DEG network, and these genes were also suppressed under high-altitude stress. As a post-transcriptional regulation mechanism, alternative splicing (AS) is ubiquitous in Tibetan sheep. High-altitude stress induced 917 differentially alternative splicing (DAS) events. High-altitude stress modulated DAS in an AS-type-specific manner: suppressing skipped exon events but increasing retained intron events. C₂H₂-type zinc finger transcription factors and RNA processing factors were mainly enriched in DAS. These findings revealed high-altitude stress repressed ovarian development by suppressing the gene expression of LH/FSH hormone signaling genes and inducing intron retention of C₂H₂-type zinc finger transcription factors.

The Qinghai Province of China is located in the northeast region of the Qinghai–Tibetan Plateau (QTP) and carries abundant yak genetic resources. Previous investigations of archaeological records, mitochondrial DNA, and Y chromosomal markers have suggested that Qinghai was the major center of yak domestication. In the present study, we examined the genomic diversity, differentiation, and selection signatures of 113 Qinghai yak, including 42 newly sequenced Qinghai yak and 71 publicly available individuals, from nine yak breeds/populations (wild, Datong, Huanhu, Xueduo, Yushu, Qilian, Geermu, Tongde, and Huzhu white) using high-depth whole-genome resequencing data. We observed that most of Qinghai yak breeds/populations have abundant genomic diversity based on four genomic parameters (nucleotide diversity, inbreeding coefficients, linkage disequilibrium decay, and runs of homozygosity). Population genetic structure analysis showed that Qinghai yak have two lineages with two ancestral origins and that nine yak breeds/populations are clustered into three distinct groups of wild yak, Geermu yak, and seven other domestic yak breeds/populations. F_ST values showed moderate genetic differentiation between wild yak, Geermu yak, and the other Qinghai yak breeds/populations. Positive selection signals were detected in candidate genes associated with disease resistance (CDK2AP2, PLEC, and CYB5B), heat stress (NFAT5, HSF1, and SLC25A48), pigmentation (MCAM, RNF26, and BOP1), vision (C1QTNF5, MFRP, and TAX1BP3), milk quality (OPLAH and GRINA), neurodevelopment (SUSD4, INSYN1, and PPP1CA), and meat quality (ZRANB1), using the integrated PI, composite likelihood ratio (CLR), and F_ST methods. These findings offer new insights into the genetic mechanisms underlying target traits in yak and provide important information for understanding the genomic characteristics of yak breeds/populations in Qinghai.

Qaidam cattle (CDM) are indigenous breed inhabiting Northwest China. In the present study, we newly sequenced 20 Qaidam cattle to investigate the copy number variants (CNVs) based on the ARS-UMD1.2 reference genome. We generated the CNV region (CNVR) datasets to explore the genomic CNV diversity and population stratification. The other four cattle breeds (Xizang cattle, XZ; Kazakh cattle, HSK; Mongolian cattle, MG; and Yanbian cattle, YB) from the regions of North China embracing 43 genomic sequences were collected and are distinguished from each of the other diverse populations by deletions and duplications. We also observed that the number of duplications was significantly more than deletions in the genome, which may be less harmful to gene formation and function. At the same time, only 1.15% of CNVRs overlapped with the exon region. Population differential CNVRs and functional annotations between the Qaidam cattle population and other cattle breeds revealed the functional genes related to immunity (MUC6), growth (ADAMTSL3), and adaptability (EBF2). Our analysis has provided numerous genomic characteristics of some Chinese cattle breeds, which are valuable as customized biological molecular markers in cattle breeding and production.

Wild yak (Bos mutus) is a vulnerable bovine species on the Qinghai–Tibetan Plateau (QTP). So far, most studies on molecular genetic diversity of wild yak have focused on autosomal and mtDNA variations based on small number of samples. In this study, we analyzed 84 D-loop and 24 whole mitogenome sequences of wild yak to further comprehensively explore its maternal genetic diversity and lineage composition. Meanwhile, using six yak Y-specific polymorphic markers (i.e., SRY4, USP9Y, UTY19, AMELY3, OFD1Y10 and INRA189), we assessed the paternal genetic diversity and lineage composition based on eight wild yak. Our results showed that wild yak exhibited abundant maternal genetic diversity with haplotype diversities of 0.9621 ± 0.0078 and 0.9928 ± 0.0144 in the D-loop and whole mitogenome sequences, respectively. Maternal phylogenetic analysis of wild yak uncovered three defined lineages (mt-I, mt-II and mt-III). Similarly, profuse paternal genetic diversity was observed in wild yak with Y-haplotype diversity (Hd) at 0.8214 ± 0.1007. Two Y-haplogroups (Y1 and Y2) with four Y-haplotypes (yH1-yH4) were identified in paternal phylogenetic analysis, indicating wild yak to be of two paternal lineages. This study of genetic diversity and lineage composition of wild yak would provide useful information for the genetic resource conservation and utilization of this vulnerable wild species.

The white yak, a type of unique and valuable farm animals on the Qinghai-Tibet Plateau, are mainly distributed in Tianzhu (County of Gansu Province), Menyuan, Huzhu and Ledu (three Counties of Qinghai Province) in China. In the present study, the Y-chromosomal genetic diversity, differentiation and phylogeny of three Chinese white yak breeds/populations (Tianzhu, Huzhu and Menyuan) were comprehensively explored using five Y-SNPs (SRY4, USP9Y, UTY19, AMELY3 and OFD1Y10) and one Y-STR (INRA189) markers. The results showed that six Y-haplotypes (H1Y1, H9Y1, H10Y1, H11Y2, H12Y2 and H13Y2) were identified in 97 male yak from three white yak breeds/populations. Among these haplotypes, H1Y1, H10Y1 and H11Y2 were shared by all of breeds/populations and H12Y2 was shared by Tianzhu and Huzhu populations. However, H9Y1 and H13Y2 haplotypes were only detected in Menyuan and Tianzhu white yak populations, respectively. The Y-haplotype diversity was maximum in Huzhu white yak (0.7500 ± 0.0349), the medium in Tianzhu white yak (0.6881 ± 0.0614) and the lowest in Menyuan white yak (0.5720 ± 0.0657). The total Y-haplotype diversity of three white yak breeds/populations was 0.7567 ± 0.0233, indicating rich paternal genetic diversity in white yak. The F_ST values showed a moderate differentiation between Tianzhu and Menyuan (F_ST = 0.0763, P < 0.05) populations, but a weak differentiation between Huzhu and Tianzhu white yak breeds/populations (F_ST = 0.0186, P > 0.05) and Huzhu and Menyuan (F_ST = − 0.005, P > 0.05) populations. The clustering analysis revealed a close genetic relationship between Huzhu and Menyuan white yak, both were far from Tianzhu white yak breed. The phylogenetic analyses showed that white yak had two Y-haplogroups/lineages (Y1 and Y2) with two potential paternal origins. The findings of present study provide new insight into the basic information for the formulation of molecular breeding programs of white yak. Moreover, it also contributes to the conservation and utilization of this special animal genetic resource.