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. 2015 Jun;200(2):619-31.
doi: 10.1534/genetics.115.176677. Epub 2015 Apr 24.

Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli

Rohan Maddamsetti  1 , Richard E Lenski  1 , Jeffrey E Barrick  2
Affiliations

Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli

Rohan Maddamsetti et al. Genetics. 2015 Jun.

Abstract

Twelve replicate populations of Escherichia coli have been evolving in the laboratory for >25 years and 60,000 generations. We analyzed bacteria from whole-population samples frozen every 500 generations through 20,000 generations for one well-studied population, called Ara-1. By tracking 42 known mutations in these samples, we reconstructed the history of this population's genotypic evolution over this period. The evolutionary dynamics of Ara-1 show strong evidence of selective sweeps as well as clonal interference between competing lineages bearing different beneficial mutations. In some cases, sets of several mutations approached fixation simultaneously, often conveying no information about their order of origination; we present several possible explanations for the existence of these mutational cohorts. Against a backdrop of rapid selective sweeps both earlier and later, two genetically diverged clades coexisted for >6000 generations before one went extinct. In that time, many additional mutations arose in the clade that eventually prevailed. We show that the clades evolved a frequency-dependent interaction, which prevented the immediate competitive exclusion of either clade, but which collapsed as beneficial mutations accumulated in the clade that prevailed. Clonal interference and frequency dependence can occur even in the simplest microbial populations. Furthermore, frequency dependence may generate dynamics that extend the period of coexistence that would otherwise be sustained by clonal interference alone.

Keywords: asexual populations; beneficial mutations; clonal interference; experimental evolution; frequency-dependent selection; mutational cohorts.

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Figures

Figure 1
Figure 1
Dynamics of mutant alleles during a long-term evolution experiment with E. coli. (A) The Muller plot shows estimated frequencies of 42 mutations in population Ara−1 over 20,000 generations. Mutations are identified by the gene in which they occurred or, if intergenic, by the adjacent genes; trailing numbers indicate that the same gene had multiple alleles. Labels preceded by a dot indicate the mutation fixed in the population, as indicated by its presence on the line of descent leading to sequenced clones from 30,000 and 40,000 generations. Genotypes of 90 clones sampled at (B) 7500 and (C) 10,000 generations, showing previously fixed and variable alleles only. Each row in each panel represents a clone. Mutations are colored as in A; light gray fill shows the mutation is not present (i.e., the clone has the ancestral allele), and white fill indicates missing data. Mutations labeled with the blue + symbol were detected in the clones sampled at 10,000 generations but not at 7500 generations.
Figure 2
Figure 2
Hypothetical scenario showing the interplay between negative frequency dependence and ongoing beneficial mutations. (A) Null case, in which the fitness of clade C2 relative to clade C1 is independent of their relative frequencies. (B) Static negative frequency dependence, where the fitness of C2 relative to C1 declines as the frequency of C2 in the population increases. (C) Dynamic frequency dependence, where ongoing mutations in each clade provide generic fitness benefits. Although the mutations do not affect the frequency-dependent interaction per se, they affect the location and existence of the stable equilibrium. In the example shown here, the first beneficial mutation (green line) occurs in C1 and lowers the equilibrium frequency of C2; the second beneficial mutation (blue line) occurs in C2 and raises its equilibrium frequency; and a third beneficial mutation (red line) occurs in C1 that eliminates the equilibrium and drives C2 extinct.
Figure 3
Figure 3
Changing nature of interaction between clones from two clades over time. (A) Clonal isolates from clades C1 and C2 sampled from population Ara−1 at 7500 generations show no frequency-dependent interaction. Although they differ by at least nine mutations, there is no significant difference in their fitness at any of the three initial ratios tested. (B) Clonal isolates from the same clades at 10,000 generations show a strong negative frequency-dependent interaction, with the fitness of the C2 clone declining as its frequency increases. The C2 clone has a significant advantage at all three initial ratios tested, although there may be a stable equilibrium with C2 at a frequency above those tested. Although C2 eventually drove C1 extinct, ongoing beneficial mutations evidently affected the dynamics (Figure 1A). Error bars show 95% confidence intervals.
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