How do the fitness effects of several mutations combine? Despite its simplicity, this question is central to the understanding of multilocus evolution. Epistasis (the interaction between alleles at different loci), especially epistasis for fitness traits such as reproduction and survival, influences evolutionary predictions1,2 “almost whenever multilocus genetics matters”3. Yet very few models4,5 have sought to predict epistasis, and none has been empirically tested. Here we show that the distribution of epistasis can be predicted from the distribution of single mutation effects, based on a simple fitness landscape model6. We show that this prediction closely matches the empirical measures of epistasis that have been obtained for Escherichia coli7 and the RNA virus vesicular stomatitis virus8. Our results suggest that a simple fitness landscape model may be sufficient to quantitatively capture the complex nature of gene interactions. This model may offer a simple and widely applicable alternative to complex metabolic network models, in particular for making evolutionary predictions.
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We thank D. Waxman and P. Jarne for comments on this work. G.M. thanks J. Goudet for hosting him during part of this work. This work was supported by an Action Concertée Incitative from the French Ministry of Research (T.L.), a PhD fellowship from the French Ministry of Research (G.M.), the Swiss National Science Foundation (grant 31-108194/1 to G.M.) and the Spanish Ministerio de Educación y Ciencia (MEC)-FEDER grant BMC2003-00066 to S.F.E.
The authors declare no competing financial interests.
Power curves for the tests shown in Table 1. (PDF 134 kb)
Robustness of the model to non-additivity in the phenotypic effects of mutations. (PDF 56 kb)
Agreement of the predicted approximate distributions with simulations. (PDF 384 kb)
Parameter estimation for the MCMC fit. (PDF 29 kb)
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Martin, G., Elena, S. & Lenormand, T. Distributions of epistasis in microbes fit predictions from a fitness landscape model. Nat Genet 39, 555–560 (2007). https://doi.org/10.1038/ng1998
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