Recently, we demonstrated that yeast protein evolutionary rate at the level of individual amino acid residues scales linearly with degree of solvent accessibility. This residue-level structure-evolution relationship is sensitive to protein core size: surface residues from large-core proteins evolve much faster than those from small-core proteins, while buried residues are equally constrained independent of protein core size. In this work, we investigate the joint effects of protein core size and expression on the residue-level structure-evolution relationship. At the whole-protein level, protein expression is a much more dominant determinant of protein evolutionary rate than protein core size. In contrast, at the residue level, protein core size and expression both have major impacts on protein structure-evolution relationships. In addition, protein core size and expression influence residue-level structure-evolution relationships in qualitatively different ways. Protein core size preferentially affects the non-synonymous substitution rates of surface residues compared to buried residues, and has little influence on synonymous substitution rates. In comparison, protein expression uniformly affects all residues independent of degree of solvent accessibility, and affects both non-synonymous and synonymous substitution rates. Protein core size and expression exert largely independent effects on protein evolution at the residue level, and can combine to produce dramatic changes in the slope of the linear relationship between residue evolutionary rate and solvent accessibility. Our residue-level findings demonstrate that protein core size and expression are both important, yet qualitatively different, determinants of protein evolution. These results underscore the complementary nature of residue-level and whole-protein analysis of protein evolution.

• PMID: 23056364
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Journal Article | Research Support, U.S. Gov't, Non-P.H.S.

Authors

Franzosa EA, Xia Y

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