Spontaneous mutation rate is a plastic trait associated with population density across many domains of life

Spontaneous genetic mutations occur during DNA replication and cell division and is a process deeply embedded in evolution. As we at GEITP have previously discussed, mutagenesis is also central in causing bacterial antibiotic resistance to drugs as well as cancer cell resistance to chemotherapeutic agents. Mutation rate can also vary at a particular site in a particular genetic locus, dependent upon the environment. Mutation rates can increase with endogenous and exogenous factors; any factor affecting the balance between mutation formation and DNA repair can modify the mutation rate. These factors include intracellular nucleotide pools, age of the organism, and anything affecting the expression and/or stochastic presence or absence of low-copy-number repair proteins.

Where such mutation/repair-balance factors depend on the environment, the result is mutation-rate plasticity. Pliable mutation rates have been most thoroughly addressed for stress-induced mutagenesis –– this may involve induction of error-prone polymerases, for instance, in the E. coli SOS response. Authors [see attached article] have recently identified a novel mode of mutation-rate plasticity in response to population density in E. coli. This plasticity does not have any blatantly obvious association with stress, because the densest populations, which experience the most competition, are those showing the lowest mutation rates. This observation of an inverse plastic association between mutation rate and population density was found at one locus in one 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.

Herein [see attached], authors address all three questions. They identified 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 from all domains of life and viruses. Furthermore, authors tested 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. The degree of plasticity was found to vary, even among closely related organisms. In each domain tested, DAMP requires proteins scavenging the mutagenic oxidized nucleotide 8-oxo-dGTP. Having accounted for other known factors affecting mutation rate, controlling for population density can lower variation in mutation-rate estimates by 93%. Widespread DAMP –– which authors manipulated genetically in disparate organisms –– also provides a novel trait to use in the fight against 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.

PloS Biol Aug 2o17; 15: e2002731

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