Ovis aries Raw sequence reads
The sheep were introduced to the high-altitude Qinghai-Tibet plateau only around 3,000 years ago.The selected breed, Tibetan sheep, which are well adapted to this alpine environment, serve as anideal model for studying the underlying genetic changes within this short time. In the present study,we investigated genomic structural variants (SVs) and their frequencies that distinguish Tibetansheep from the low-altitude Hu sheep. We discovered highly contrasting frequencies of SVsassociated with genes involved in heart development, blood vessel development, and circulationbetween the two breeds. We identified 462 genes with highly-frequent allelic SVs, includingEPAS1, PAPSS2, and PTPRD in Tibetan sheep. Single-cell RNA-Seq data revealed the SVssignificantly influenced the expression levels of these three genes in specific cells responsive tohypoxia, consistent with the results obtained from luciferase reporter assay. Of particular interestis the identification of a large inversion with modified chromatin architectures in Tibetan sheep,which contains several genes with altered expression patterns related to heart protection, brownadipose generation, angiogenesis and DNA repair. These findings indicate a specific role for theseSVs and related genes in high-altitude adaptation during the artificial selection of Tibetan sheep.Our study highlights the influence of genomic SVs on high-altitude adaptation in sheep andprovides additional markers for breeding high-altitude breeds in the future.