The Environment Affects Epistatic Interactions to Alter the Topology of an Empirical Fitness Landscape

<div><p>The fitness effect of mutations can be influenced by their interactions with the environment, other mutations, or both. Previously, we constructed 32 ( = 2⁵) genotypes that comprise all possible combinations of the first five beneficial mutations to fix in a laboratory-evolved population of <i>Escherichia coli</i>. We found that (i) all five mutations were beneficial for the background on which they occurred; (ii) interactions between mutations drove a diminishing returns type epistasis, whereby epistasis became increasingly antagonistic as the expected fitness of a genotype increased; and (iii) the adaptive landscape revealed by the mutation combinations was smooth, having a single global fitness peak. Here we examine how the environment influences epistasis by determining the interactions between the same mutations in two alternative environments, selected from among 1,920 screened environments, that produced the largest increase or decrease in fitness of the most derived genotype. Some general features of the interactions were consistent: mutations tended to remain beneficial and the overall pattern of epistasis was of diminishing returns. Other features depended on the environment; in particular, several mutations were deleterious when added to specific genotypes, indicating the presence of antagonistic interactions that were absent in the original selection environment. Antagonism was not caused by consistent pleiotropic effects of individual mutations but rather by changing interactions between mutations. Our results demonstrate that understanding adaptation in changing environments will require consideration of the combined effect of epistasis and pleiotropy across environments.</p></div

Distributions of epistatic effects in two environments.

<p>Observed and expected fitness were compared for 26 genotypes containing two or more mutations in two environments. Absolute epistasis was calculated as described in the text.</p

The five mutations in the order in that they arose and fixed in a population of <i>E. coli</i> from Lenski et al. 2002.

*<p> Relative fitness in DM25, experimental evolution conditions, relative to the ancestor, REL606.</p>1<p><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426-Cooper2" target="_blank">[39]</a>, </p>2<p><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426-Crozat1" target="_blank">[62]</a>, </p>3<p><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426-Pelosi1" target="_blank">[65]</a>, </p>4<p><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426-Lenski4" target="_blank">[66]</a>, </p>5<p><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426-Stanek1" target="_blank">[61]</a>, </p>6<p><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426-Schneider1" target="_blank">[57]</a>.</p

The magnitude and direction of epistatic effects on growth vary with external environment.

<p>Symbols represent growth (AUC) of a particular genotype relative to the ancestor (triangles = gp, circles = rtsgp). Filled symbols represent expected relative growth and open symbols represent observed relative growth based on a multiplicative model assuming no epistatic interactions. Differences between observed and expected values were determined using the t statistic (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426.s013" target="_blank">Table S9</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003426#pgen.1003426.s014" target="_blank">S10</a>).</p

Relationship between relative epistasis and expected fitness assuming no epistasis in each foreign environment.

<p>Each point refers to one of the 32 genotypes assayed for fitness in both environments (a, EGTA, b, guanazole). Error bars represent the standard deviation approximated through the method of error propagation. The solid lines are the best linear fit with the text below reporting the correlation (<i>r</i>) and significance (<i>P</i> values).</p

Effects of beneficial mutations in alternative environments.

<p>Genotypes are designated as single letters and define alleles: <i>rbs</i> (r), <i>topA</i> (t), <i>spot</i> (s), <i>glmS</i> (g), and <i>pykF</i> (p). Fill color defines the environment: black, DM25, white, EGTA, and grey, guanazole. Mutational effects were determined to depend on the environment using an ANOVA. Asterisks represent significance based on a <i>P</i> value < 0.05.</p