- THIS ARTICLE
- Full Text
- Full Text (PDF)
-
All Versions of this Article:
genetics.106.061754v1
175/1/255 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Email this article to a friend
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Bloom, J. D.
- Articles by Wilke, C. O.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Bloom, J. D.
- Articles by Wilke, C. O.
Originally published as Genetics Published Articles Ahead of Print on November 16, 2006.
Genetics, Vol. 175, 255-266, January 2007, Copyright © 2007
doi:10.1534/genetics.106.061754
Thermodynamics of Neutral Protein Evolution
Jesse D. Bloom*,1,
Alpan Raval
and
Claus O. Wilke
* Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, Keck Graduate Institute of Applied Life Sciences and School of Mathematical Sciences, Claremont Graduate University, Claremont, California 91711 and Section of Integrative Biology and Center for Computational Biology and Bioinformatics, University of Texas, Austin, Texas 78712
1 Corresponding author: Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 210-41, 1200 E. California Blvd., Pasadena, CA 91125.
E-mail: jesse.bloom{at}gmail.com
Naturally evolving proteins gradually accumulate mutations while continuing to fold to stable structures. This process of neutral evolution is an important mode of genetic change and forms the basis for the molecular clock. We present a mathematical theory that predicts the number of accumulated mutations, the index of dispersion, and the distribution of stabilities in an evolving protein population from knowledge of the stability effects (
G values) for single mutations. Our theory quantitatively describes how neutral evolution leads to marginally stable proteins and provides formulas for calculating how fluctuations in stability can overdisperse the molecular clock. It also shows that the structural influences on the rate of sequence evolution observed in earlier simulations can be calculated using just the single-mutation G values. We consider both the case when the product of the population size and mutation rate is small and the case when this product is large, and show that in the latter case the proteins evolve excess mutational robustness that is manifested by extra stability and an increase in the rate of sequence evolution. All our theoretical predictions are confirmed by simulations with lattice proteins. Our work provides a mathematical foundation for understanding how protein biophysics shapes the process of evolution.
This article has been cited by other articles:
 |
|
 |
|
  J. D. Bloom and F. H. Arnold In the Light of Evolution III: Two Centuries of Darwin Sackler Colloquium: In the light of directed evolution: Pathways of adaptive protein evolution PNAS, June 16, 2009; 106(Supplement_1): 9995 - 10000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Bull and C. O. Wilke Lethal Mutagenesis of Bacteria Genetics, October 1, 2008; 180(2): 1061 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Bedford and D. L. Hartl Overdispersion of the Molecular Clock: Temporal Variation of Gene-Specific Substitution Rates in Drosophila Mol. Biol. Evol., August 1, 2008; 25(8): 1631 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bedford, I. Wapinski, and D. L. Hartl Overdispersion of the Molecular Clock Varies Between Yeast, Drosophila and Mammals Genetics, June 1, 2008; 179(2): 977 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Zeldovich, P. Chen, and E. I. Shakhnovich Protein stability imposes limits on organism complexity and speed of molecular evolution PNAS, October 9, 2007; 104(41): 16152 - 16157. [Abstract] [Full Text] [PDF]
|
|