Article

Distributions of epistasis in microbes fit predictions from a fitness landscape model

University of Lausanne, Lausanne, Vaud, Switzerland
Nature Genetics (Impact Factor: 29.65). 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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Available from: Santiago F Elena, Aug 27, 2015
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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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    • "The second component follows the distribution of neutral epistasis for traits. This can be approximated by a normal distribution with mean and variance (Martin et al. 2007). The first component is the product of two independent random variables following the distribution given by (S2a). "
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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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