Normal Mutation Rate Variants Arise in a Mutator (Mut S) Escherichia coli Population

Abstract

The rate at which mutations are generated is central to the pace of evolution. Although this rate is remarkably similar amongst all cellular organisms, bacterial strains with mutation rates 100 fold greater than the modal rates of their species are commonly isolated from natural sources and emerge in experimental populations. Theoretical studies postulate and empirical studies teort the hypotheses that these “mutator” strains evolved in response to selection for elevated rates of generation of inherited variation that enable bacteria to adapt to novel and/or rapidly changing environments. Less clear are the conditions under which selection will favor reductions in mutation rates. Declines in rates of mutation for established populations of mutator bacteria are not anticipated if such changes are attributed to the costs of augmented rates of generation of deleterious mutations. Here we report experimental evidence of evolution towards reduced mutation rates in a clinical isolate of Escherichia coli with an hyper-mutable phenotype due a deletion in a mismatch repair gene, (ΔmutS). The emergence in a ΔmutS background of variants with mutation rates approaching those of the normal rates of strains carrying wild-type MutS was associated with increase in fitness with respect to ancestral strain. We postulate that such an increase in fitness could be attributed to the emergence of mechanisms driving a permanent “aerobic style of life”, the negative consequence of this behavior being regulated by the evolution of mechanisms protecting the cell against increased endogenous oxidative radicals involved in DNA damage, and thus reducing mutation rate. Gene expression assays and full sequencing of evolved mutator and normo-mutable variants supports the hypothesis. In conclusion, we postulate that the observed reductions in mutation rate are coincidental to, rather than, the selective force responsible for this evolution.

Metabolic Erosion Primarily Through Mutation Accumulation, and Not Tradeoffs, Drives Limited Evolution of Substrate Specificity in Escherichia coli

“…Recent findings have suggested that mutators may tend to attenuate their increased mutation rate over time [16],[54],[55], perhaps to avoid the harmful effects of Muller's Ratchet. Thus both tradeoffs in alternative environments and mutation load in selective environments may contribute to the paradox that over the short term lineages often benefit from elevated mutation rates, but the long-term trend across phylogenies has been for stability in mutation rates of free-living microbes [56].…”

Experimental evolution and the dynamics of genomic mutation rate modifiers

“…Tröbner and Piechocki were unable to characterize either the genetic basis or the population dynamics of the modifier(s) responsible for decreasing the mutation rate but showed that the mutT allele itself had not changed. Clones with lower mutation rates have also been isolated from mutS mutator populations of E. coli after experimental colonization of the mouse gut (Giraud et al, 2001) and in vitro propagation by serial passaging (Turrientes et al, 2013). Another recent example of such short-term selection against strong mutator phenotypes is provided by the work of Loh et al (2010), who co-propagated 66 E. coli strains with different mutation rates for 350 generations: moderate-strength mutators were most favored in all of their experimental populations.…”

“…A recent study in Pseudomonas aeruginosa also showed that a mutS mutator allele can provide inherent resistance to oxidative stress and so could have a direct fitness benefit in certain environments (Torres- Barceló et al, 2013). On the other hand, a different study in mutS E. coli populations has documented the appearance of apparently directly beneficial variants with lower mutation rates (Turrientes et al, 2013). In general, it is conceivable that mutation rate modifiers can have pleiotropic effects on fitness that affect their propensity to spread in natural populations, but at present it is unclear whether such effects would contribute to stabilizing the mutation rate at the low wild-type levels that prevail in most natural populations.…”

Fixation probability of rare nonmutator and evolution of mutation rates

“…2012; Turrientes et al. 2013; Wielgoss et al. 2013), the mutation rate of an adapted population carrying a mutator allele has been seen to decrease and the time to fixation has been measured, but a theoretical understanding of this time scale is missing.…”