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Why highly expressed proteins evolve slowly

Drummond, D. Allan and Bloom, Jesse D. and Adami, Christoph and Wilke, Claus O. and Arnold, Frances H. (2005) Why highly expressed proteins evolve slowly. Proceedings of the National Academy of Sciences of the United States of America, 102 (40). pp. 14338-14343. ISSN 0027-8424. PMCID PMC1242296.

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Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons that have remained unexplained. Here, we hypothesize that selection to reduce the burden of protein misfolding will favor protein sequences with increased robustness to translational missense errors. Pressure for translational robustness increases with expression level and constrains sequence evolution. Using several sequenced yeast genomes, global expression and protein abundance data, and sets of paralogs traceable to an ancient whole-genome duplication in yeast, we rule out several confounding effects and show that expression level explains roughly half the variation in Saccharomyces cerevisiae protein evolutionary rates. We examine causes for expression's dominant role and find that genome-wide tests favor the translational robustness explanation over existing hypotheses that invoke constraints on function or translational efficiency. Our results suggest that proteins evolve at rates largely unrelated to their functions and can explain why highly expressed proteins evolve slowly across the tree of life.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Bloom, Jesse D.0000-0003-1267-3408
Adami, Christoph0000-0002-2915-9504
Wilke, Claus O.0000-0002-7470-9261
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2005 by the National Academy of Sciences Edited by Francisco J. Ayala, University of California, Irvine, CA, and approved August 11, 2005 (received for review May 16, 2005). Published online before print September 21, 2005, 10.1073/pnas.0504070102 This work was supported by National Institutes of Health National Research Service Award 5 T32 MH19138 (to D.A.D.) and a Howard Hughes Medical Institute Predoctoral Fellowship (to J.D.B.). Author contributions: D.A.D. designed and performed research; D.A.D., J.D.B., C.A., C.O.W., and F.H.A. contributed new reagents/analytic tools; D.A.D. analyzed data; and D.A.D., J.D.B., C.A., C.O.W., and F.H.A. wrote the paper. This paper was submitted directly (Track II) to the PNAS office.
Funding AgencyGrant Number
NIH Predoctoral Fellowship5 T32 MH19138
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:evolutionary rate, protein misfolding, yeast, translation errors, gene duplication
Issue or Number:40
PubMed Central ID:PMC1242296
Record Number:CaltechAUTHORS:DRUpnas05b
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2221
Deposited By: Archive Administrator
Deposited On:21 Mar 2006
Last Modified:02 Oct 2019 22:51

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