Maximum likelihood analysis of mammalian p53 indicates the presence of positively selected sites and higher tumorigenic mutations in purifying sites

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Abstract

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.

Details

Authors
External organisations
  • External Organization - Unknown
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry

Keywords

  • p53, Phylogenetic analysis, Maximum likelihood
Original languageEnglish
Pages (from-to)29-35
JournalGene
Volume483
Issue number1-2
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)

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