Selection Signatures at PRLR and Heat Shock Protein Genes Reveal the Genetic Basis of Heat Stress Adaptation in Cattle

Background: Heat stress is a critical constraint to cattle productivity, health, and reproductive efficiency in tropical and subtropical regions, with severity increasing under climate change. Indigenous Bos indicus cattle display superior thermotolerance compared with high-producing Bos taurus breeds, yet the genomic basis of this adaptation remains incompletely resolved. Genes regulating endocrine signaling and cellular stress responses particularly the prolactin receptor (PRLR) and heat shock protein (HSP) families are strong candidates for heat stress adaptation. Methods: High-density SNP genotype data were analyzed from five cattle breeds representing contrasting climatic adaptation: Sahiwal, Cholistani, Brahman, Holstein Friesian, and Jersey. Population structure was examined using principal component analysis and model-based ancestry inference. Genetic differentiation was quantified using pairwise fixation index (FST) estimates. Genome-wide selection signatures were detected using a sliding-window FST approach (50 kb windows, 10 kb step size), and candidate regions were functionally annotated to identify genes associated with thermoregulation and cellular stress response. Results: Clear genetic separation between Bos indicus and Bos taurus breeds was observed, with low differentiation among indigenous cattle. Genome-wide scans revealed multiple regions exceeding the 99th and 99.9th percentile thresholds of the FST distribution, indicating strong selection signals. Prominent signatures were detected at the PRLR locus and within key heat stress–related genes, including HSPB1, HSPA1A, HSF1, ATP2B1, and FGF5. Several highly polymorphic SNPs within PRLR were located in intronic and nested gene regions, suggesting potential regulatory roles influencing endocrine signaling and cellular homeostasis under heat stress. Conclusion: This study provides compelling genomic evidence that selection at PRLR and heat shock protein genes forms a central genetic basis for heat stress adaptation in cattle. The identified loci offer robust targets for marker-assisted and genomic selection. Incorporation of these markers into national breeding programs and livestock policies can accelerate the development of climate-resilient cattle populations, strengthen conservation of indigenous genetic resources, and enhance the long-term sustainability of dairy and beef production systems under rising global temperatures.