Fig. 4

Site-specific positive selection in p53 protein. P53 sequences of 65 mammalian species were analyzed using models implemented by PAML, Selecton, and HyPhy tools (a). Significant positively-selected sites are marked with blue and presented on the relevant positions of Spalax p53 sequence. (In PAML: probability (omega >1) >0.95* or >0.99**; in Selecton: lower bound of the confidence table >1; in Hyphy: p-value ≤ 0.05* or ≤0.01**, proportion ≥ 0.05). Positions composing stress-related patterns E49, A52, L381 in Spalax p53 (corresponding to D48, E51 and L383 in human p53, respectively) are marked with pink; b Examples of protein-protein interactions presumably affected by changes in positions which compose the stress-related patterns and signals for positive selection (dN/dS >1). Left and middle panels - positions in p53 TAD/RD (cyan) in complex with CBP, Sir2, and p62 proteins (green), as modeled for human p53. Residues D48 and E51 are in balls and are illustrated in p53 interactions with p62 (PDBID 2RUK) and CBP (PDBID 2 L14) via TAD2. Position L383 is illustrated in balls in p53 in complex with Sir2 (PDBID 1MA3) and CBP (PDBID 1JSP) via RD. The indicated positions participate in the binding by mediating hydrophobic and ionic interactions (Table 2). An additional position that was identified as positively selected by all tested models (right panel, marked in yellow) in p53 DBD (A129, human p53) is illustrated in the human model (PDBID 2MEJ) of p53 (blue) in complex with Bcl-xL (purple)