A relationship between the functional significance of individual amino acid residues of the p53 protein, their positions in the protein structure, and the mode of evolution of the codons corresponding to these residues has been established. A phylogenetic analysis of the coding sequences of the gene of p53 from 32 vertebrate species has been performed. It was found that those codons undergo selection that affect the efficiency of binding of protein p53 as a transcription factor. It was shown that the frequency of occurrence of generative mutations maintaining the normal function of the protein in conservative codons differs statistically significantly from the frequency of occurrence in the same codons of mutations with the effects of loss and acquisition of the function, and the negatively dominant effect. The phylogenetic analysis and molecular dynamics modeling made it possible to obtain evidence for the functional significance of the G245 residue for which the appearance of the binding site for Zn2+ in the case of the substitution G245G has previously been proposed.

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