Epistasis and frequency dependence influence the fitness of an adaptive mutation in a diversifying lineage

Abstract

The opportunity for a mutation to invade a population can dramatically vary depending on the context in which this mutation occurs. Such context dependence is difficult to document as it requires the ability to measure how a mutation affects phenotypes and fitness and to manipulate the context in which the mutation occurs. We identified a mutation in a gene encoding a global regulator in one of two ecotypes that diverged from a common ancestor during 1200 generations of experimental evolution. We replaced the ancestral allele by the mutant allele, and vice versa, in several clones isolated during the time course of the evolution experiment, and compared the phenotype and fitness of clones isogenic except for the focal mutation. We show that the fitness and phenotype of the mutation are strongly affected by epistatic interactions between genes in the same genome, as well as by frequency dependent selection resulting from biotic interactions between individuals in the same population. We conclude that amongst the replicate population in which it spread, the mutation we identified is only adaptive when occurring in specific genomes and competing with specific individuals. This study thus demonstrates that the opportunity for an adaptive mutation to spread in an evolutionary lineage can only be understood in the light of its genomic and competitive environments.

Parallel Evolutionary Dynamics of Adaptive Diversification in Escherichia coli

“…In population 18, for which the timeline of metabolic phenotypes has been documented [28], the rapid rise of these mutations corresponds very well with the increase in the mean switching lag shown in Figure 1B of Spencer et al [28]. Similarly, in population 20, SS bacteria were present by generation 200 [31]. In both cases, spoT and rbs were the only SS-associated mutations present when the SS phenotype was first detected, so one or both of these mutations must have caused the SS phenotype.…”

“…Here we experimentally address the first of these issues using asexual organisms, in which mating does not lead to recombination between diverging subpopulations, and which are therefore ideally suited to study the ecological conditions generating the frequency dependence necessary for adaptive diversification. Indeed, adaptive diversification has been documented in microbial evolution experiments [11],[12],[27]–[31] in which well-mixed populations of Escherichia coli bacteria founded with a single genotype repeatedly evolve two metabolically distinct phenotypes. When grown in well-mixed serial batch cultures in medium with glucose and acetate as carbon sources, E. coli cells preferentially metabolize glucose and excrete acetate until the glucose is depleted and then undergo a diauxic switch to acetate consumption [32].…”

Can You Sequence Ecology? Metagenomics of Adaptive Diversification

“…For example, the authors of the present study suggest nadR alleles in the SS lineages were beneficial only after the FS lineage arose. Alternatively, since the nadR alleles consistently rose after the Δ rbs and spoT mutations occurred in their own lineage, perhaps their benefit was modified by earlier mutations in their lineage, as has been found in other studies [17],[26],[27] including one of the authors' own [25]. So did nadR alleles arise because of between-organism coevolution, within-genome epistasis, both of these effects, or neither of them?…”

“…One of the key advantages of this study is the backdrop of a rich history of earlier papers that characterized parallel diversification across replicate populations that evolved in a mixture of glucose and acetate [22]–[25]. Their ancestral strain grows quickly on glucose, and then slowly switches to eating the much less desirable acetate.…”

“…Furthermore, both the likelihood of FS emerging [24] and the benefit of particular mutations within this lineage [25] have been shown to depend upon whether the SS phenotype had already evolved. Some of the genetic basis of these phenotypes had been worked out previously [23],[25], and this paper extends these analyses by first sequencing a dozen isolates representing known SS or FS phenotypes from three populations. The major data, however, was metagenomic sequencing of time series to test whether raw sequence data could capture that adaptive diversification took place.…”