Article

Martin G, Elena SF, Lenormand T. Distributions of epistasis in microbes fit predictions from a fitness landscape model. Nature Genet 39: 555-560

University of Lausanne, Lausanne, Vaud, Switzerland
Nature Genetics (Impact Factor: 29.35). 05/2007; 39(4):555-60. DOI: 10.1038/ng1998
Source: PubMed

ABSTRACT

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 predictions "almost whenever multilocus genetics matters". Yet very few models 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 model. We show that this prediction closely matches the empirical measures of epistasis that have been obtained for Escherichia coli and the RNA virus vesicular stomatitis virus. 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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    • "From this initial use in theories of adaptation , the FGM can also serve as a null model to fit and interpret empirical DFEs. Indeed, this model was shown to capture the DFE of single mutants (Martin and Lenormand 2006b), of epistasis (Martin et al. 2007) or of dominance (Manna et al 2011). With respect to environmental effects, which is our focus here, (Martin and Lenormand 2006a) showed that mutation accumulation data was consistent with a concave, nearly Gaussian phenotype-fitness function with constant shape and varying optima across environments . "
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    • "anjuan and Elena , 2006 ; Martin et al . , 2007 ; Aylor and Zeng , 2008 ; Perfeito et al . , 2011 ; Walkiewicz et al . , 2012 ) . Indeed , studies of whole viruses , bacteria etc . have revealed more epistasis among mutations than studies looking at the protein level ( Bonhoeffer et al . , 2004 ; Michalakis and Roze , 2004 ; Segre et al . , 2005 ; Martin et al . , 2007 ; Kryazhimskiy et al . , 2011 ; Breen et al . , 2012 ; Kachanovsky et al . , 2012 ; Kouyos et al . , 2012 ; Flynn et al . , 2013 ) . However even in a simplified model of enzyme evolution , in which enzymatic activity in the cell is directly related to fitness ( as is the case for essential metabolic enzymes or antibiotic resistance mar"
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    • "This is a pure effect of dimensionality on hybrid fitness, which occurs even when controlling for the effect on the overall selection strength, as measured by s 0 (Fig. 2). Note that e i j is also a measure of the pairwise fitness epistasis between mutations in FGM (Martin et al. 2007). Hence in this model, the hybrid load can be expressed in terms of the mean epistasis between mutations fixed within each population, rather than different populations as for classic DMI. "
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