title: Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau.
abstract: Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau.
authors.affiliation: Division of Neurobiology and Physiology, Department of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Ren
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.forename: Sheng-Ting
authors.initials: ST
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Cao
authors.forename: Hu-Yue
authors.initials: HY
authors.lastname: Zu
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Chen
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Wu
authors.forename: Eviatar
authors.initials: E
authors.lastname: Nevo
authors.forename: Xue-Qun
authors.initials: XQ
authors.lastname: Chen
authors.forename: Ji-Zeng
authors.initials: JZ
authors.lastname: Du
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D003411:Arvicolinae / Q000235:genetics* / Q000378:metabolism; D003080:Cold Temperature; D019143:Evolution, Molecular; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics*; D018609:Tibet; D015533:Transcriptional Activation / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Apaf1; Noxa; Puma; ecological stress; evolution