Abstract
Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis—SIM) and decrease at high final population density (density-associated mutation-rate plasticity—DAMP). We hypothesised that these two forms of mutation-rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM results in a mutation rate minimum at intermediate nutrient levels (which can support 7 × 108 cells ml−1). These findings demonstrate a strikingly close and nuanced relationship of ecological factors—stress and population density—with mutation, the fuel of all evolution.
Highlights
How and why the rate of spontaneous genetic mutation varies is a fundamental and enduring biological issue [1]
We assayed mutation rates to rifampicin resistance using fluctuation tests in E. coli K-12 MG1655 grown across a gradient of nutrient availability: a range of concentrations (1–90% vol/vol) of lysogeny broth (LB) mixed with Davis minimal (DM) medium (LB/DM)
We find that the relationship of mutation rate to LB concentration is non-linear (Fig. 1a, likelihood ratio test of a quadratic effect of log nutrient availability on log mutation rate: N = 97, LR8,7 = 105, P = 1.2 × 10−24, model S-I in Supplementary Information)
Summary
How and why the rate of spontaneous genetic mutation varies is a fundamental and enduring biological issue [1]. Extreme shifts in temperature or various DNA-damaging agents [4] In these environments, double-stranded breaks can induce stress responses that in turn increase mutation rates via DNA polymerases with different error rates [5]—a phenomenon known as stress-induced mutagenesis (SIM). We found that, across microbes, the mutation rate of a particular genotype is closely associated with the final density to which the population grows (D, i.e. the carrying capacity of the environment divided by its volume) [6]. In this so-called density-associated mutation-rate plasticity (DAMP), bacterial and yeast populations show a power law (log–log linear) reduction in mutation rate with D when grown in a defined minimal medium with glucose as the sole carbon source [6, 7]. Differences in the underlying mechanism and the fact that the densest populations, experiencing the highest stress, show the lowest mutation rates, suggest that DAMP is not obviously associated with stress
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