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MBE Advance Access published online on June 7, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm118
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Letter

Mutational Reversions During Adaptive Protein Evolution

Mark A. DePristo1,*, Daniel L. Hartl1 and Daniel M. Weinreich1,2

1 Department of Organismic and Evolutionary Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138
2 Current address: Department of Ecology and Evolutionary Biology, and Center for Computational Molecular Biology, Brown University, Providence, RI 02912

* To whom correspondence should be addressed. Email: mark_depristo{at}harvard.edu, Fax: +1 (617) 496-5854, Phone: +1 (617) 496-5540

Received for publication January 22, 2007. Revision received May 29, 2007. Accepted for publication June 4, 2007.

Adaptation is often regarded as the sequential fixation of individually, intrinsically beneficial mutations. Contrary to this expectation, we find a surprisingly large number of evolutionary trajectories on which natural selection first favors a mutation, then favors its removal, and later still favors its ultimate restoration during the course of antibiotic resistance evolution. The existence of reversion trajectories implies that natural selection may not follow the most parsimonious path separating two allles, even during adaptation. Altogether, this discovery highlights the unusual and potentially circuitoius routes natural selection can follow during adaptation.

Key Words: Adaptation • reversion • evolution • protein • gene • mutation


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