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MBE Advance Access published online on January 29, 2007

Molecular Biology and Evolution, doi:10.1093/molbev/msm019
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Proportion of Solvent-Exposed Amino Acids in a Protein and Rate of Protein Evolution

Yeong-Shin Lin1,2, Wei-Lun Hsu3, Jenn-Kang Hwang1,3 and Wen-Hsiung Li2

1 Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan 300
2 Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, Illinois 60637, USA
3 Institute of Bioinformatics, National Chiao Tung University, Hsinchu, Taiwan 300

Corresponding author: Wen-Hsiung Li, Email: whli{at}uchicago.edu

Corresponding author: Jenn-Kang Hwang, Email: jkhwang{at}cc.nctu.edu.tw

Accepted for publication January 22, 2007.

Translational selection, including gene expression, protein abundance, and codon usage bias, has been suggested as the single dominant determinant of protein evolutionary rate in yeast. Here we show that protein structure is also an important determinant. Buried residues, which are responsible for maintaining protein structure or are located on a stable interaction surface between two subunits, are usually under stronger evolutionary constraints than solvent-exposed residues. Our partial correlation analysis shows that, when whole proteins are included, the variance of evolutionary rate explained by the proportion of exposed residues (Pexposed) can reach two-thirds of that explained by translational selection, indicating that Pexposed is the most important determinant of protein evolutionary rate next only to translational selection. Our result suggests that proteins with many residues under selective constraint (e.g. maintaining structure or intermolecular interaction) tend to evolve slowly, supporting the "fitness (functional) density" hypothesis.


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