Historical Contingency Causes Divergence in Adaptive Expression of the lac Operon

Abstract

Populations of Escherichia coli selected in constant and fluctuating environments containing lactose often adapt by substituting mutations in the lacI repressor that cause constitutive expression of the lac operon. These mutations occur at a high rate and provide a significant benefit. Despite this, eight of 24 populations evolved for 8,000 generations in environments containing lactose contained no detectable repressor mutations. We report here on the basis of this observation. We find that, given relevant mutation rates, repressor mutations are expected to have fixed in all evolved populations if they had maintained the same fitness effect they confer when introduced to the ancestor. In fact, reconstruction experiments demonstrate that repressor mutations have become neutral or deleterious in those populations in which they were not detectable. Populations not fixing repressor mutations nevertheless reached the same fitness as those that did fix them, indicating that they followed an alternative evolutionary path that made redundant the potential benefit of the repressor mutation, but involved unique mutations of equivalent benefit. We identify a mutation occurring in the promoter region of the uspB gene as a candidate for influencing the selective choice between these paths. Our results detail an example of historical contingency leading to divergent evolutionary outcomes.

Mutational robustness changes during long-term adaptation in laboratory budding yeast populations

“…The picture that emerges from our data is one in which idiosyncratic epistatic effects are largely unpredictable but have biases that often lead to correlations with background fitness. In both our own work and other studies of microbial evolution, these biases are more often towards negative epistasis: beneficial mutations tend to have negative epistatic interactions with both deleterious (Johnson et al, 2019, this study) and beneficial mutations (Chou et al, 2011; Hall et al, 2019; Karkare et al, 2021; Khan et al, 2011; Kryazhimskiy et al, 2014; Ono et al, 2017; Pearson et al, 2012; Perfeito et al, 2014; Rokyta et al, 2011; Wünsche et al, 2017).…”

“…Beneficial mutations can be redundant by inactivating the same deleterious pathway (e.g., ADE pathway mutations discussed above), solving the same general problem (e.g., mutations shortening lag in Karkare et al, 2021), or changing a phenotype with a nonlinear fitness function (Chiu et al, 2012;Chou et al, 2014;Keren et al, 2016;Lunzer et al, 2005;Otwinowski et al, 2018). Nonmonotonic fitness functions can arise from phenotypes with both potential benefits and costs (Dekel and Alon, 2005), such that negative interactions between beneficial mutations and the benefit can lead to fitness-correlated epistasis that crosses neutrality, exhibiting diminishing returns, increasing costs, and sign epistasis (Figure 3 -figure supplement 1).…”

“…These studies have found that beneficial mutations isolated from laboratory evolution experiments tend to exhibit negative epistasis. That is, they are less beneficial in combination than would be expected from the combination of their effects in isolation (Karkare et al, 2021;MacLean et al, 2010;Ono et al, 2017;Rokyta et al, 2011;Schenk et al, 2013;Schoustra et al, 2016;Zee and Velicer, 2017). However, some examples of positive epistasis among beneficial mutations have also been observed (Chou et al, 2009;Fumasoni and Murray, 2020;Hsieh et al, 2020;Khan et al, 2011;Levin-Reisman et al, 2019).…”

“…By looking at the effects of insertion mutations in these strains, we are measuring a panel of hidden phenotypes that may change predictably or stochastically during evolution. The widespread presence of epistasis observed in biological systems suggests that these hidden phenotypes may be important to long-term evolutionary outcomes as the fitness effects of mutations effectively open and close doors to unique pathways for evolution (Johnson et al, 2021; Karkare et al, 2021; Kvitek and Sherlock, 2011).…”

Hybrid de novo Genome Assembly of Erwinia sp. E602 and Bioinformatic Analysis Characterized a New Plasmid-Borne lac Operon Under Positive Selection

“…The lac operon is a hallmark gene of the regulatory circuit for bacteria to regulate metabolism according to nutrient conditions in the environment (Leonard et al, 2015;Malakar, 2015;Karkare et al, 2021;Pinto et al, 2021). Through genome function annotation, a large number of genes related to lactose metabolism were found in Erwinia sp.…”