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Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding

Wilke, Claus O. and Lenski, Richard E. and Adami, Christoph (2003) Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding. BMC Evolutionary Biology, 3 (3). ISSN 1471-2148. http://resolver.caltech.edu/CaltechAUTHORS:WILbcmeb03

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Abstract

Background: The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed. Results: We studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances. Conclusions: Our findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes.


Item Type:Article
Additional Information: © 2003 Wilke et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. COW was responsible for the RNA folding simulations and the data analysis. All authors contributed substantially to the design of the study and the writing of the manuscript. All authors read and approved the final manuscript. We thank Charles Ofria and Michael D. Stern for stimulating discussions, and Sergey Gavrilets for constructive criticism on an earlier version of this work. This research was supported by the National Science Foundation under Contract No. DEB-9981397. Part of this work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.
Subject Keywords:RNA secondary structure folding, synergistic epistasis, antagonistic epistasis, compensatory mutations
Record Number:CaltechAUTHORS:WILbcmeb03
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:WILbcmeb03
Alternative URL:http://dx.doi.org/10.1186/1471-2148-3-3
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:994
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:22 Nov 2005
Last Modified:26 Dec 2012 08:42

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