From the inside out : determining sequence conservation within the context of relative solvent accessibility
Scherrer, Michael Paul
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Evolutionary rates vary vastly across intraspecific genes and the determinants of these rates is of central concern to the field of comparative genomics. Tradition has held that preservation of protein function conserved the sequence, however mounting evidence implicates the biophysical properties of proteins themselves as the elements that constrain sequence evolution. Of these properties, the exposure of a residue to solvent is the most prevalent determinant of its evolutionary rate due to pressures to maintain proper synthesis and folding of the structure. In this work, we have developed a model that considers the microenvironment of a residue in the estimation of its evolutionary rate. By working within the structural context of a protein's residues, we show that our model is better able to capture the overall evolutionary trends affecting conservation of both the coding sequences and the protein structures from a genomic level down to individual genes.