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Significance This work explores the environmental correlates of variations in codon 104 of thep53 gene in three mammalian species: two subterranean mammals, highland- and lowland-dwelling wild zokors (Myospalax baileyi andMyospalax cansus , respectively), and one highland-dwelling aboveground species, the root vole (Microtus oeconomus ). InMicrotus oeconomus the codon 104E variation inp53 suppresses apoptotic gene reactivation and cell apoptosis. In contrast, inM .baileyi the codon104N variation is responsible for the transactivation of apoptotic genes under three environmental stresses—hypoxia, hypercapnia (acidic stress, high CO2 ), and cold temperature—that characterize its ecological niche in the Tibet plateau. We conclude that p53 in nature is adapted in structure and function in accordance with specific ecological stresses.

Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau