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Background  Life at high altitude results in physiological and metabolic challenges that put strong evolutionary pressure on performance due to oxidative stress, UV radiation and other factors dependent on the natural history of the species. To look for genes involved in altitude adaptation in a large herbivore, this study explored genome differentiation between a feral population of Andean horses introduced by the Spanish in the 1500s to the high Andes and their Iberian breed relatives.    Results  Using allelic genetic models and Fst analyses of ~50 K single nucleotide polymorphisms (SNPs) across the horse genome, 131 candidate genes for altitude adaptation were revealed (Bonferoni of  p  ≤ 2 × 10 –7 ). Significant signals included the  EPAS1  in the hypoxia-induction-pathway (HIF) that was previously discovered in human studies ( p  = 9.27 × 10 -8 ); validating the approach and emphasizing the importance of this gene to hypoxia adaptation. Strong signals in the cytochrome P450 3A gene family ( p  = 1.5 ×10 -8 ) indicate that other factors, such as highly endemic vegetation in altitude environments are also important in adaptation. Signals in tenuerin 2 ( TENM2, p  = 7.9 × 10 -14 ) along with several other genes in the nervous system (gene categories representation  p  = 5.1 × 10 -5 ) indicate the nervous system is important in altitude adaptation.    Conclusions  In this study of a large introduced herbivore, it becomes apparent that some gene pathways, such as the HIF pathway are universally important for high altitude adaptation in mammals, but several others may be selected upon based on the natural history of a species and the unique ecology of the altitude environment.

A genome wide study of genetic adaptation to high altitude in feral Andean Horses of the páramo