Zheng Wangshan, Ge Siyu, Zhang Zehui, Li Ying, Li Yuxing, Leng Yan, Wang Yiming, Kang Xiaohu, Wang Xinrong
School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou 730070, China.
Provincial R&D Institute of Ruminants in Gansu, Lanzhou 730070, China.
Genes (Basel). 2025 Jul 29;16(8):909. doi: 10.3390/genes16080909.
: Complete environmental adaptation requires both survival and reproductive success. The hypoxic Qinghai-Tibet Plateau (>3000 m) challenges reproduction in indigenous species. Tibetan sheep, a key plateau-adapted breed, possess remarkable hypoxic tolerance, yet the genetic basis of their reproductive success remains poorly understood. : We integrated transcriptomic and genomic data from Tibetan sheep and two lowland breeds (Small-tailed Han sheep and Hu sheep) to identify Tibetan sheep reproduction-associated genes (TSRGs). : We identified 165 TSRGs: four genes were differentially expressed (DEGs) versus Small-tailed Han sheep, 77 DEGs versus Hu sheep were found, and 73 genes were annotated in reproductive pathways. Functional analyses revealed enrichment for spermatogenesis, embryonic development, and transcriptional regulation. Notably, three top-ranked selection signals (, , and ) showed differential expression. Murine Gene Informatics (MGI) confirmed that knockout orthologs exhibit significant phenotypes including male infertility, abnormal meiosis (male/female), oligozoospermia, and reduced neonatal weight. : Tibetan sheep utilize an evolved suite of genes underpinning gametogenesis and embryogenesis under chronic hypoxia, ensuring high reproductive fitness-a vital component of their adaptation to plateaus. These genes provide valuable genetic markers for the selection, breeding, and conservation of Tibetan sheep as a critical genetic resource.
完全的环境适应需要生存和繁殖成功。缺氧的青藏高原（海拔>3000米）对本土物种的繁殖构成挑战。藏羊是适应高原的关键品种，具有显著的缺氧耐受性，但其繁殖成功的遗传基础仍知之甚少。
我们整合了藏羊以及两个低地品种（小尾寒羊和湖羊）的转录组和基因组数据，以鉴定藏羊繁殖相关基因（TSRGs）。
我们鉴定出165个TSRGs：与小尾寒羊相比，有4个基因差异表达（DEGs）；与湖羊相比，发现77个DEGs，并且有73个基因在生殖途径中被注释。功能分析显示精子发生、胚胎发育和转录调控显著富集。值得注意的是，三个排名靠前的选择信号（、和）显示出差异表达。小鼠基因信息学（MGI）证实，敲除直系同源基因会表现出显著的表型，包括雄性不育、减数分裂异常（雄性/雌性）、少精子症和新生儿体重减轻。
藏羊利用一套在慢性缺氧条件下支持配子发生和胚胎发生的进化基因，确保了高繁殖适应性——这是它们适应高原的重要组成部分。这些基因为藏羊作为关键遗传资源的选择、育种和保护提供了有价值的遗传标记。
