Local packing density is the main structural determinant of the rate of protein sequence evolution at site level - PubMed (original) (raw)

Local packing density is the main structural determinant of the rate of protein sequence evolution at site level

So-Wei Yeh et al. Biomed Res Int. 2014.

Abstract

Functional and biophysical constraints result in site-dependent patterns of protein sequence variability. It is commonly assumed that the key structural determinant of site-specific rates of evolution is the Relative Solvent Accessibility (RSA). However, a recent study found that amino acid substitution rates correlate better with two Local Packing Density (LPD) measures, the Weighted Contact Number (WCN) and the Contact Number (CN), than with RSA. This work aims at a more thorough assessment. To this end, in addition to substitution rates, we considered four other sequence variability scores, four measures of solvent accessibility (SA), and other CN measures. We compared all properties for each protein of a structurally and functionally diverse representative dataset of monomeric enzymes. We show that the best sequence variability measures take into account phylogenetic tree topology. More importantly, we show that both LPD measures (WCN and CN) correlate better than all of the SA measures, regardless of the sequence variability score used. Moreover, the independent contribution of the best LPD measure is approximately four times larger than that of the best SA measure. This study strongly supports the conclusion that a site's packing density rather than its solvent accessibility is the main structural determinant of its rate of evolution.

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Figures

Figure 1

Figure 1

Comparison of sequence variability profiles by their average Pearson's correlation coefficients with different structural profiles. The sequence variability scores (listed in the figure legend) are ConSurf rate of evolution (CS), Evolutionary Trace score (ET), Karlin & Brocchieri Sum-of-Pairs score (KBSP), Valdar & Thornton Sum-of-Pairs score (VTSP), and Entropy (EN). The structural properties (the apices of the hexagon) are Weighted Contact Number (WCN), Contact Number (CN), Relative Solvent Accessibility (RSA), and Absolute Solvent Accessibility (ASA). The asterisk mark on CN means that the cut-off radius was chosen to maximize each CN-sequence average correlation. The cut-off radii for CS, ET, KBSP, VTSP, and EN are 19 Å, 19 Å, 18 Å, 18 Å, and 20 Å, respectively. Superscript letters distinguish RSA profiles obtained using different methods.

Figure 2

Figure 2

Comparison of structural profiles by their average Pearson's correlation coefficients with different sequence variability profiles. The sequence variability measures (the axes of the pentagon) are ConSurf rate of evolution (CS), Evolutionary Trace score (ET), Karlin & Brocchieri Sum-of-Pairs score (KBSP), Valdar & Thornton Sum-of-Pairs score (VTSP), and Entropy (EN). The structural properties (listed in the figure legend) are Weighted Contact Number (WCN), Contact Number (CN), Relative Solvent Accessibility (RSA), and Absolute Solvent Accessibility (ASA). The asterisk mark on CN means that the cut-off radius was chosen to maximize each CN-sequence average correlation. The cut-off radii for CS, ET, KBSP, VTSP, and EN are 19 Å, 19 Å, 18 Å, 18 Å, and 20 Å, respectively. Superscript letters distinguish RSA profiles obtained using different methods.

Figure 3

Figure 3

Local packing density versus solvent accessibility as determinants of site-specific evolutionary rates. Points above (below) the diagonal are proteins for which WCN (RSAT) correlates better than RSAT (WCN) with the site-specific rates of amino acid substitution as estimated using the phylogenetic-based approach ConSurf (CS). The percentages of points above and below the diagonals are shown.

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References

    1. Pál C, Papp B, Lercher MJ. An integrated view of protein evolution. Nature Reviews Genetics. 2006;7(5):337–348. - PubMed
    1. Thorne JL. Protein evolution constraints and model-based techniques to study them. Current Opinion in Structural Biology. 2007;17(3):337–341. - PubMed
    1. Worth CL, Gong S, Blundell TL. Structural and functional constraints in the evolution of protein families. Nature Reviews Molecular Cell Biology. 2009;10(10):709–720. - PubMed
    1. Wilke CO, Drummond DA. Signatures of protein biophysics in coding sequence evolution. Current Opinion in Structural Biology. 2010;20(3):385–389. - PMC - PubMed
    1. Grahnen JA, Nandakumar P, Kubelka J, Liberles DA. Biophysical and structural considerations for protein sequence evolution. BMC Evolutionary Biology. 2011;11(1, article 361) - PMC - PubMed

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