Identification and in silico impact assessment of missense mutations in key genes associated with hypoxic stress in Changthangi goats

Abstract

In order to enhance breeding programs and boost genetic features related to disease resistance, productivity and adaptability, it is essential to predict harmful mutations in livestock animals. The genetic adaptations enabling Changthangi goats to thrive in high-altitude environments are essential for their survival in conditions marked by hypoxia, extreme temperatures and oxidative stress. Therefore, in this study, missense mutations were mined within key candidate genes, namely CXCL9, MRPL22 and SDS involved in hypoxic stress, in Changthangi goats to assess their potential effects on the structural integrity of the proteins. Two SNPs (rs653275315, rs654804090) were identified with significant impacts on protein structure and stability, while one SNP (rs644425445) was categorized as benign. The SNP rs654804090 introduced changes in hydrophobicity, impairing protein stability, whereas rs653275315 affected conserved domains critical for function. Structural analyses revealed that the identified mutations disrupted protein folding, stability and molecular interactions, particularly in highly conserved residues, underscoring their evolutionary significance. Phylogenetic conservation analysis further highlighted the adaptive relevance of these mutations, particularly in regions subjected to environmental stressors. Our findings reveal potentially detrimental mutations in the genes CXCL9, MRPL22 and SDS, which may contribute to the development of genetic screening tools for selective breeding initiatives especially in high-altitude settings where genetic resistance to environmental stress is essential.