Site-Specific Structural Constraints on Protein Sequence Evolutionary Divergence: Local Packing Density versus Solvent Exposure

So-Wei Yeh, Jen-Wei Liu, Sung-Huan Yu, Chien Hua Shih, Jenn-Kang Hwang, Julian Echave

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Protein sequences evolve under selection pressures imposed by functional and biophysical requirements, resulting in site-dependent rates of amino acid substitution. Relative solvent accessibility (RSA) and local packing density (LPD) have emerged as the best candidates to quantify structural constraint. Recent research assumes that RSA is the main determinant of sequence divergence. However, it is not yet clear which is the best predictor of substitution rates. To address this issue, we compared RSA and LPD with site-specific rates of evolution for a diverse data set of enzymes. In contrast with recent studies, we found that LPD measures correlate better than RSA with evolutionary rate. Moreover, the independent contribution of RSA is minor. Taking into account that LPD is related to backbone flexibility, we put forward the possibility that the rate of evolution of a site is determined by the ease with which the backbone deforms to accommodate mutations.
Original languageEnglish
Pages (from-to)135-139
Number of pages5
JournalMolecular Biology and Evolution
Volume31
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • protein evolution; site-specific evolutionary rate; protein structure; local packing density; contact number; weighted contact number; relative solvent accessibility
  • CONSERVATION; ACCESSIBILITY; BIOPHYSICS; ALIGNMENT; PATTERN; VIEW

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