Domestication and subsequent selection of cattle to form breeds and biological types that can adapt to different environments partitioned ancestral genetic diversity into distinct modern lineages. Genome-wide selection particularly for adaptation to extreme environments left detectable signatures genome-wide. We used high-density genotype data for 42 cattle breeds and identified the influence of Bos grunniens and Bos javanicus on the formation of Chinese indicine breeds that led to their divergence from India-origin zebu. We also found evidence for introgression, admixture, and migration in most of the Chinese breeds. Selection signature analyses between high-altitude (≥1800 m) and low-altitude adapted breeds (<1500 m) revealed candidate genes (ACSS2 , ALDOC, EPAS1 , EGLN1, NUCB2) and pathways that are putatively involved in hypoxia adaptation. Immunohistochemical, real-time PCR and CRISPR/cas9 ACSS2 -knockout analyses suggest that the up-regulation of ACSS2 expression in the liver promotes the metabolic adaptation of cells to hypoxia via the hypoxia-inducible factor pathway. High altitude adaptation involved the introgression of alleles from high-altitude adapted yaks into Chinese Bos taurus taurus prior to their formation into recognized breeds and followed by selection. In addition to selection, adaptation to high altitude environments has been facilitated by admixture and introgression with locally adapted cattle populations. • 42 taurine and indicine breeds and 3 yak breeds were genotyped using 777KSNP assay. • Introgression, admixture and migration were found in most of Chinese cattle breeds. • B. grunniens and B. javanicus introgressions caused divergence of indicine breeds. • Selection signatures revealed candidate genes involved in hypoxia adaptation. • Introgressed ACSS2 promotes adaptation to hypoxia via HIF pathway. [ABSTRACT FROM AUTHOR]