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Structural Determinants of the Rate of Protein Evolution in Yeast

Bloom, Jesse D. and Drummond, D. Allan and Arnold, Frances H. and Wilke, Claus O. (2006) Structural Determinants of the Rate of Protein Evolution in Yeast. Molecular Biology and Evolution, 23 (9). pp. 1751-1761. ISSN 0737-4038. doi:10.1093/molbev/msl040.

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We investigate how a protein's structure influences the rate at which its sequence evolves. Our basic hypothesis is that proteins with highly designable structures (structures that are encoded by many sequences) will evolve more rapidly. Recent theoretical advances argue that structures with a higher density of interresidue contacts are more designable, and we show that high contact density is correlated with an increased rate of sequence evolution in yeast. In addition, we investigate the correlations between the rate of sequence evolution and several other structural descriptors, carefully controlling for the strong effect of expression level on evolutionary rate. Overall, we find that the structural descriptors that we consider appear to explain roughly 10% of the variation in rates of protein evolution in yeast. We also show that despite the well-known trend for buried residues to be more conserved, proteins with a higher fraction of buried residues, nonetheless, tend to evolve their sequences more rapidly. We suggest that this effect is due to the increased designability of structures with more buried residues. Our results provide evidence that protein structure plays an important role in shaping the rate of sequence evolution and provide evidence to support recent theoretical advances linking structural designability to contact density.

Item Type:Article
Related URLs:
URLURL TypeDescription
Bloom, Jesse D.0000-0003-1267-3408
Arnold, Frances H.0000-0002-4027-364X
Wilke, Claus O.0000-0002-7470-9261
Additional Information:© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. Accepted June 13, 2006; Advance Access publication June 16, 2006. J.D.B. was supported by a Howard Hughes Medical Institute predoctoral fellowship, and C.O.W. was supported by National Institutes of Health grant AI 065960.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHAI 065960
Subject Keywords:designability, protein structure, evolutionary rate, protein evolution, principal component regression, yeast
Issue or Number:9
Record Number:CaltechAUTHORS:20180925-124255575
Persistent URL:
Official Citation:Jesse D. Bloom, D. Allan Drummond, Frances H. Arnold, Claus O. Wilke; Structural Determinants of the Rate of Protein Evolution in Yeast, Molecular Biology and Evolution, Volume 23, Issue 9, 1 September 2006, Pages 1751–1761,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89919
Deposited By: Tony Diaz
Deposited On:25 Sep 2018 21:53
Last Modified:16 Nov 2021 00:39

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