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

• DOI: 10.1073/pnas.1320369110
• Publication Date: 2013-12-03T04:57:30Z
• Authors: Yang Zhao; Ji-Long Ren; Ming-Yang Wang; Sheng-Ting Zhang; Yu Liu; Min Li; Yi-Bin Cao; Hu-Yue Zu; Xiao-Cheng Chen; Chung-I Wu; Eviatar Nevo; Xue-Qun Chen; Ji-Zeng Du
• Keywords: Transcriptional Activation; 0301 basic medicine; 0303 health sciences; Arvicolinae; Apoptosis; 15. Life on land; Tibet; Adaptation, Physiological; Cold Temperature; Evolution, Molecular; 03 medical and health sciences; Stress, Physiological; Animals; Humans; Tumor Suppressor Protein p53; Hypoxia

Significance

This work explores the environmental correlates of variations in codon 104 of the p53 gene in three mammalian species: two subterranean mammals, highland- and lowland-dwelling wild zokors ( Myospalax baileyi and Myospalax cansus , respectively), and one highland-dwelling aboveground species, the root vole ( Microtus oeconomus ). In Microtus oeconomus the codon 104E variation in p53 suppresses apoptotic gene reactivation and cell apoptosis. In contrast, in M . baileyi the codon104N variation is responsible for the transactivation of apoptotic genes under three environmental stresses—hypoxia, hypercapnia (acidic stress, high CO 2 ), 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.