Genetic analysis of cold tolerance and high-altitude adaptation in Gannan indigenous Tibetan sheep through genome-wide scans

Understanding the genetic basis of adaptation to extreme environments is crucial in evolutionary biology. Gannan Tibetan sheep, which thrive in high altitudes with thin air and cold climates, demonstrate remarkable resilience. However, the genetic basis of their adaptations remains poorly understood. In this study, we conducted whole-genome resequencing of three indigenous Tibetan sheep breeds, including Ganjia (n = 12), Oula (n = 12), Kecai (n = 12), from the Gannan Tibetan Autonomous Prefecture (average altitude of 3,500 m) in China. By integrating our data with previously published genomic data of sheep from northern China (Altitude below 1,500 m), we examined the genetic population structure, ancestry components, and signatures of positive selection. Our analyses, including principal component analysis, neighbor-joining tree construction, and ADMIXTURE, revealed that the three indigenous Tibetan sheep breeds share a common ancestry with other Tibetan sheep breeds, yet exhibit distinct population differentiation. Moreover, all three breeds display high genetic diversity, which enhances their adaptation to harsh local environments. Through selective sweep analysis, we identified genes associated with cold tolerance and high-altitude adaptation. These genes are involved in mitochondrial function and oxidative stress (LONP1, NDUFA11, NDUFB4 and HSD11B1L), cardiorespiratory and vascular function (FECH, TNFAIP3), and fat metabolism and thermogenesis (ACSL6, PDGFD, CES3, MTCH2, TMEM8B, SPAG8, ETAA1, ZIC1, ATG5, and HAO2). Additionally, we identified candidate regions containing genes related to immunity and physical traits. This study provides a comprehensive overview of the genomic variations, ancestry compositions, and selective signals linked to high-altitude traits in Gannan indigenous Tibetan sheep. Our findings offer valuable insights into the breeding and management of Tibetan sheep.