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Evolution favors protein mutational robustness in sufficiently large populations

Bloom, Jesse D. and Lu, Zhongyi and Chen, David and Raval, Alpan and Venturelli, Ophelia S. and Arnold, Frances H. (2007) Evolution favors protein mutational robustness in sufficiently large populations. BMC Biology, 5 (29). ISSN 1741-7007. PMCID PMC1995189.

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Background: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. Results: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by mathematical theory, and can be quantitatively related to the way that the proteins occupy their neutral network. Conclusions: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations.

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URLURL TypeDescription CentralArticle
Bloom, Jesse D.0000-0003-1267-3408
Arnold, Frances H.0000-0002-4027-364X
Additional Information:© 2007 Bloom et al., licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Submission date 12 March 2007; Acceptance date 17 July 2007; Publication date 17 July 2007. Authors’ contributions: JDB and FHA designed the project and wrote the paper. JDB and ZL performed the bulk of the experiments; OSV assisted with the experiments. JDB and DC analyzed the data. JDB and AR performed the theoretical work. All authors read and approved the final manuscript. Acknowledgements: We thank Claus O Wilke for helpful advice and comments. JDB is supported by a HHMI predoctoral fellowship. ZL and DC were supported by Summer Undergraduate Research Fellowships from the California Institute of Technology. AR is supported by NSF grants CCF 0523643 and FIBR 0527023.
Issue or Number:29
PubMed Central ID:PMC1995189
Record Number:CaltechAUTHORS:BLObmcb07
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8380
Deposited By: Archive Administrator
Deposited On:02 Aug 2007
Last Modified:02 Oct 2019 23:50

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