African zebu cattle (Bos indicus) exhibit remarkable adaptations to extreme thermal conditions, yet the genomic basis of this resilience remains incompletely characterized. Ethiopia provides a unique natural setting in which closely related zebu populations have adapted divergently to dry-hot (DHETZ) and humid-hot (HHETZ) climates. In this study, we reanalyzed publicly available whole-genome sequencing datasets from 46 Ethiopian zebu cattle from five populations and compared them with Asian zebu, Sudanese zebu, African taurine, and European taurine breeds. By integrating genome-wide SNP analysis, population genetic structure assessment, and multiple selection scans (iHS, Hp, XP-EHH, and XP-CLR), we identified distinct and shared selection signatures between DHETZ and HHETZ. We detected 33.7 million and 34.2 million biallelic autosomal SNPs in DHETZ and HHETZ, respectively. Ethiopian zebu clustered closely with Sudanese zebu but showed clear divergence from Asian zebu and taurine breeds. DHETZ and HHETZ exhibited very low genetic differentiation (FST = 0.0063), consistent with their shared ancestry; however, each group displayed unique selection signals. In DHETZ, iHS and Hp detected 298 and 113 candidate regions, respectively, whereas in HHETZ, they detected 244 and 138 regions, respectively. Cross-population XP-EHH and XP-CLR analyses identified 163 and 227 divergent regions between DHETZ and HHETZ, respectively. Integration of the four selection scans identified 19 high-confidence candidate regions in DHETZ and 13 in HHETZ. DHETZ showed strong selection in genes involved in oxidative stress regulation, protein folding, mitochondrial function, and vascular remodeling, including SESN2, DNAJC8, GRPEL2, ABLIM3, and AFAP1L1. In contrast, HHETZ displayed signatures in genes associated with immune responses, energy metabolism, and angiogenesis inhibition, including MYD88, PRKACA, PRKACB, and WIF1. Several genes, including VEGFC, TNIP3, and DMXL2, were under selection in both groups, suggesting conserved mechanisms of thermotolerance and reproductive adaptation. The shared VEGFC signal and the HHETZ-specific WIF1 signal may indicate a distinct vascular regulatory mechanism in the dry-hot and humid-hot environments. Our results reveal a dual pattern of genomic adaptation in Ethiopian zebu cattle and provide candidate loci for future validation and climate-resilient livestock breeding.
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