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A Single Determinant Dominates the Rate of Yeast Protein Evolution

Drummond, D. Allan and Raval, Alpan and Wilke, Claus O. (2006) A Single Determinant Dominates the Rate of Yeast Protein Evolution. Molecular Biology and Evolution, 23 (2). pp. 327-337. ISSN 0737-4038. doi:10.1093/molbev/msj038.

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A gene's rate of sequence evolution is among the most fundamental evolutionary quantities in common use, but what determines evolutionary rates has remained unclear. Here, we carry out the first combined analysis of seven predictors (gene expression level, dispensability, protein abundance, codon adaptation index, gene length, number of protein-protein interactions, and the gene's centrality in the interaction network) previously reported to have independent influences on protein evolutionary rates. Strikingly, our analysis reveals a single dominant variable linked to the number of translation events which explains 40-fold more variation in evolutionary rate than any other, suggesting that protein evolutionary rate has a single major determinant among the seven predictors. The dominant variable explains nearly half the variation in the rate of synonymous and protein evolution. We show that the two most commonly used methods to disentangle the determinants of evolutionary rate, partial correlation analysis and ordinary multivariate regression, produce misleading or spurious results when applied to noisy biological data. We overcome these difficulties by employing principal component regression, a multivariate regression of evolutionary rate against the principal components of the predictor variables. Our results support the hypothesis that translational selection governs the rate of synonymous and protein sequence evolution in yeast.

Item Type:Article
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Wilke, Claus O.0000-0002-7470-9261
Additional Information:© The Author 2005. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. MBE Advance Access originally published online on October 19, 2005 We are grateful to Frances H. Arnold for insightful comments on the manuscript. C.O.W. was supported by National Institutes of Health (NIH) grant AI 065960 and D.A.D. was supported by NIH National Research Service Award 5 T32 MH19138.
Funding AgencyGrant Number
NIHAI 065960
NIH Predoctoral Fellowship5 T32 MH19138
Subject Keywords:Saccharomyces cerevisiae, evolutionary rate, gene expression, protein-protein interactions, dispensability, translational selection
Issue or Number:2
Record Number:CaltechAUTHORS:DRUmbe06
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2222
Deposited By: Archive Administrator
Deposited On:07 Apr 2006
Last Modified:08 Nov 2021 19:46

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