CONICET | Buscador de Institutos y Recursos Humanos

Introduction The study of evolutionary rates is a central issue to understand the mechanisms underlying protein molecular evolution. Several factors have been associated to the modulation of the evolutionary rate. Gene expression level shows one of the strongest and consistent correlation with the number of nonsynonymous substitution per nonsynonymous site at codon level (dN). Different studies indicate that structure-functional features could have comparable contributions to explain evolutionary rates [refs?]. In this work we study how the presence of conformational diversity (native state as an ensemble of different conformers with similar free energy) in proteins could influence the rate of evolution. Results We found that the maximum RMSD100 (normalized root-mean-squared distance of alpha carbons to 100 aligned residues) between a pair of conformers, negatively correlates with dN for a benchmark of 401 human proteins for which both evolutionary and conformational information is available. We obtained a Spearman correlation rho of -0.16 with P value lesser than 0.005. For a sample of more than 400 (yo pondría el numero exacto, ej: 401), ,. A partial spearman rank correlation test conclude that the variables expression level and conformational diversity are significantly and independently related to evolutionary rates (coeficient rho of -0.15 and a P lesser than 5%) Conclusions There is a negative correlation between the evolutionary rate, of human´s proteins, and its conformational diversity, measured as the maximum RMSD between two conformers. This correlation is independent of protein´s expression level. Our results suggest that proteins with higher conformational diversity have additional structural constraints and as a consequence they evolve with lower rates. Our findings could have important implications in the understanding of protein evolution process.