X-linked signatures of positive selection and adaptive genetic plasticity shaping high-altitude resilience in Indian Changthangi sheep

Abstract

Recent genomic studies have focused on understanding the genetic basis of high-altitude adaptation, a classic example of evolutionary response to extreme environments. While most of these studies have concentrated on autosomal regions, the role of sex chromosomes, particularly the X chromosome, in this adaptation has been relatively unexplored. So, in this study, we performed an intensive scan of the X chromosome of Changthangi sheep as well as other Indian and exotic sheep to understand the indications of high-altitude adaptation by exploring population structure, genetic relationships, and signatures of selection on X-chromosome. Our findings reveal a close genetic affinity between Changthangi and Tibetan sheep, suggesting a shared evolutionary history that is similar to the findings of autosomal study. Additionally, we uncovered evidence of gene flow from Deccani and Australian Merino breeds into the Changthangi gene pool. Through a comprehensive analysis of selection signatures, we identified 14 candidate genes and several unannotated loci, out of which nine genes were potentially associated with high-altitude adaptation and these genes are implicated in various biological processes, including fatty acid metabolism, muscle function, potassium channel regulation, transcription, glycogen metabolism, neuronal function, RNA modification, mRNA splicing, synaptic transmission, and hypoxia response. Our study was the first to provide valuable insights into X chromosome genetic mechanisms underlying high-altitude adaptation in Changthangi sheep. These, along with autosomal findings have implications for future breeding strategies aimed at improving the resilience and productivity of Changthangi sheep in harsh environments.