Abstract
Abstract The plateau zokor (Myospalax baileyi) is a specialized subterranean rodent that lives on the Qinghai-Tibet Plateau. The species has evolved a series of strategies to adapt to its hypoxic environment and hypercapnia. p53 is a tumour suppressor gene that plays a crucial role in the cellular response to hypoxia by inducing cell cycle arrest, cell apoptosis, DNA damage repair and angiogenesis. To investigate the sequence characteristics of p53 and the response to hypoxia in plateau zokor, we cloned the p53 coding DNA sequence, analysed it, and measured the expression level of p53 at different altitudes in plateau zokor and rats. Our results show that the coding DNA sequence is 1179 bp, consisting of 392 amino acid residues. Compared to human p53, the subterranean rodents have two mutation sites in common with the human hotspots in the DNA-binding domain. Compared to subterranean rodents, plateau zokor have a mutation at residue 309. In addition, subterranean rodents have two convergent sites at residues 78 and 84. The expression levels of p53 in plateau zokor tissues increase significantly from 2260 m to 3300 m, but there was no significant difference in rats at those altitudes. Our results suggest that subterranean rodents have two mutation sites in common with the human hotspots in the DNA-binding domain, the mutation of Gly309Asp is a unique mutation site of plateau zokor p53, and there are two convergent sites enhancing subterranean rodent adaptation to hypoxic conditions. In addition, p53 is sensitive to the oxygen concentration in plateau zokor, and hypoxia upregulates the levels of p53. Generally, plateau zokor use this strategy to adapt to a hypoxic environment.
Highlights
P53, a tumour suppressor gene, plays a major role in the cellular response to DNA damage and hypoxia (Resnick & Inga, 2003; Ashur-Fabian et al, 2004; Resnick et al, 2005; Menendez et al, 2006)
Multiple sequence alignment analysis using Multalin software showed that compared with human p53, four amino acid sequences of subterranean rodents (M. baileyi, E. cansus, S. judaei, H. glaber) had seven mutation sites in common within the DNA-binding domain: Met131Leu (M131L, 133 in human – numbering by actual position; numbering of the amino acids including gaps was used for the figure), Gln163Lys (Q163K, 165 in human), Val201Ala (V201A, 203 in human), Gln246Arg (Q246R, 248 in human), Leu265Arg (L265R, 267 in human), His271Arg (H273R, 273 in human), and Leu287Phe (L287F, 289 in human)
Heterocephalus glaber belongs to the family of subterranean rodents; this species was far removed from other subterranean rodents
Summary
P53, a tumour suppressor gene, plays a major role in the cellular response to DNA damage and hypoxia (Resnick & Inga, 2003; Ashur-Fabian et al, 2004; Resnick et al, 2005; Menendez et al, 2006) It is one of the most frequently mutated proteins in cancers (Hernandez et al, 2003; Klein, 2004). The plateau zokor, Myospalax baileyi, is a specialized subterranean rodent living on the Qinghai-Tibet Plateau This species inhabits sealed burrows at an altitude of 2800 to 4200 m (Wang et al, 1979; Fan & Shi, 1982). We clone the coding DNA sequence (CDS) of p53, analyse and characterize p53 in other rodents, and measure p53’s expression differences between high and low altitudes in plateau zokor tissues using quantitative real-time PCR
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
