Introgression, admixture and selection facilitate genetic adaptation to high-altitude environments in Chinese cattle

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 (>1800m) and
low-altitude adapted breeds (<1500m) 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 suggests 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 B. t. 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.