title: Modeling coding-sequence evolution within the context of residue solvent accessibility.
abstract: BACKGROUND
  Protein structure mediates site-specific patterns of sequence divergence. In particular, residues in the core of a protein (solvent-inaccessible residues) tend to be more evolutionarily conserved than residues on the surface (solvent-accessible residues).
  
  
  RESULTS
  Here, we present a model of sequence evolution that explicitly accounts for the relative solvent accessibility of each residue in a protein. Our model is a variant of the Goldman-Yang 1994 (GY94) model in which all model parameters can be functions of the relative solvent accessibility (RSA) of a residue. We apply this model to a data set comprised of nearly 600 yeast genes, and find that an evolutionary-rate ratio ω that varies linearly with RSA provides a better model fit than an RSA-independent ω or an ω that is estimated separately in individual RSA bins. We further show that the branch length t and the transition-transverion ratio κ also vary with RSA. The RSA-dependent GY94 model performs better than an RSA-dependent Muse-Gaut 1994 (MG94) model in which the synonymous and non-synonymous rates individually are linear functions of RSA. Finally, protein core size affects the slope of the linear relationship between ω and RSA, and gene expression level affects both the intercept and the slope.
  
  
  CONCLUSIONS
  Structure-aware models of sequence evolution provide a significantly better fit than traditional models that neglect structure. The linear relationship between ω and RSA implies that genes are better characterized by their ω slope and intercept than by just their mean ω.
authors.affiliation: Center for Computational Biology and Bioinformatics, Institute for Cellular and Molecular Biology, and Section of Integrative Biology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Scherrer
authors.forename: Austin G
authors.initials: AG
authors.lastname: Meyer
authors.forename: Claus O
authors.initials: CO
authors.lastname: Wilke
mesh_terms: D003198:Computer Simulation; D019143:Evolution, Molecular; D008957:Models, Genetic; D016366:Open Reading Frames / Q000235:genetics*; D012440:Saccharomyces / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012997:Solvents
chemical_list: D012997:Solvents