Abstract
Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life.
Highlights
The probability of spontaneous genetic mutations occurring during replication evolves among organisms [1]
Spontaneous mutations fuel evolution, but the rate at which they occur can vary for a particular organism depending on its environment—a phenomenon known as mutation-rate plasticity
We identify this density-associated mutation-rate plasticity (DAMP) in data culled from the published literature: beyond well-known patterns of mutation-rate variation among organisms, we see substantial variation within diverse organisms, the large majority of which is associated with population densities
Summary
The probability of spontaneous genetic mutations occurring during replication evolves among organisms [1]. Any factor that affects the balance between mutagenesis and DNA repair can modify the mutation rate These include intracellular nucleotide pools [4], organism age [5], and factors affecting the expression [6] and stochastic presence or absence [7] of low copy number repair proteins. Where such mutation/repair-balance factors depend on the environment, the result is mutation-rate plasticity. We have recently identified a novel mode of mutation-rate plasticity in response to population density in E. coli. This plasticity does not have any very obvious association with stress—the densest populations, experiencing the most competition, show the lowest mutation rates [9]
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