Phylogenetic analysis of the p53 and p63/p73 gene families

Proteins of the relative families p53 and p63/p73 are transcriptional factors that are involved in the signaling pathway in cells. The wide spectrum of their functions includes cell cycle arrest and apoptosis in response to DNA damage. The p53 protein also participates in development of particular tissues during embryogenesis. Thus, it is of high importance to establish the relation between structure, function and evolution of these proteins. In the current computational study, the evolutionary mode of the p63/p73 protein family is investigated. Search for the adaptive branches of the phylogenetic tree and the adaptive codons in the nucleotide sequences was performed using the codem1 program from the PAML package, version 3.14. The results obtained were compared with those of our previous phylogenetic analysis of the p53 protein. Evidence was obtained that the evolutionary history of the p63/p73 proteins has been under positive selection. An attempt is made to associate the current evidence with the previous for positive selection in the p53 family. Recently the G245C substitution has been assumed to result in formation of a novel Zn(2+)-binding site in the p53 protein. The molecular mechanics simulations were performed to estimate energy of zinc binding to its site in two dominant-negative p53 mutants--G245C and R175H--in comparison with the wild-type p53. The results of the estimation provided evidence of the novel Zn(2+)-binding site functionality in G245C mutant form.