Genomic Insights into the Thermotolerance Mechanisms of Bos indicus Cattle Breeds

Heat stress poses a significant challenge to cattle production by disrupting physiological homeostasis, impairing productivity, and reducing reproductive efficiency. Genetic improvement through selective breeding for thermotolerance represents a sustainable and cost-effective mitigation strategy. To elucidate the genomic basis of heat stress adaptation in tropical cattle, we performed a comprehensive whole-genome comparative analysis of Bos indicus breeds. High-throughput sequencing identified 25,967,634 single nucleotide polymorphisms (SNPs) and 20,528,061 insertions/deletions (InDels) across the studied populations. Functional annotation of 15,456 genes harboring high-impact variants revealed critical pathways involved in cellular stress response. Notably, heat shock factor 1 ( HSF1 ) emerged as a master regulator of the heat shock response (HSR), orchestrating the expression of heat shock proteins ( HSPs ) that maintain proteostasis through molecular chaperoning, protein refolding, and degradation of irreversibly damaged proteins. Furthermore, HSF1 modulates additional stress-responsive pathways, including the unfolded protein response (UPR), antioxidant defense mechanisms, and autophagy. Protein-protein interaction network analysis identified key hub genes— GSK3B, BCL2, HSPA5, CASP3, HSP90B1, PPARG, TGFB1, MTOR, MAPK3 , and HSPA4 —implicated in thermotolerance. These findings elucidate genomic variants and mechanisms underlying thermotolerance in Bos indicus , providing targets for breeding resilient cattle in tropical climates.