Biochemistry and Molecular Biology, Jahangirnagar University, Bangladesh.
Gene. 2011 Sep 1;483(1-2):29-35. doi: 10.1016/j.gene.2011.05.011. Epub 2011 May 24.
The tumor suppressor gene TP53 (p53) maintains genome stability. Mutation or loss of p53 is found in most cancers. Analysis of evolutionary constrains and p53 mutations reveal important sites for concomitant functional studies. In this study, phylogenetic analyses of the coding sequences of p53 from 26 mammals were carried out by applying a maximum likelihood method. The results display two branches under adaptive evolution in mammals. Moreover, each codon of p53 was analyzed by the PAML method for presence of positively selected sites. PAML identified several statistically significant amino acids that undergo positive selection. The data indicates that amino acids responsible for the core functions of p53 are highly conserved, while positively selected sites are predominantly located in the N- and C-terminus of p53. Further analysis of evolutionary pressure and mutations showed the occurrence of more frequent tumorigenic mutations in purifying sites of p53.
抑癌基因 TP53（p53）维持基因组稳定性。p53 的突变或缺失存在于大多数癌症中。对进化限制和 p53 突变的分析揭示了同时进行功能研究的重要位点。在这项研究中，应用最大似然法对来自 26 种哺乳动物的 p53 编码序列进行了系统发育分析。结果显示哺乳动物中存在两个分支处于适应进化中。此外，还通过 PAML 方法分析了 p53 的每个密码子是否存在正选择位点。PAML 鉴定了几个经历正选择的统计上显著的氨基酸。数据表明，负责 p53 核心功能的氨基酸高度保守，而正选择位点主要位于 p53 的 N-和 C-末端。对进化压力和突变的进一步分析表明，p53 的纯化位点更频繁地发生致瘤突变。
