Adaptive tuning of mutation rates allows fast response to lethal stress in Escherichia coli

Abstract

While specific mutations allow organisms to adapt to stressful environments, most changes in an organism's DNA negatively impact fitness. The mutation rate is therefore strictly regulated and often considered a slowly-evolving parameter. In contrast, we demonstrate an unexpected flexibility in cellular mutation rates as a response to changes in selective pressure. We show that hypermutation independently evolves when different Escherichia coli cultures adapt to high ethanol stress. Furthermore, hypermutator states are transitory and repeatedly alternate with decreases in mutation rate. Specifically, population mutation rates rise when cells experience higher stress and decline again once cells are adapted. Interestingly, we identified cellular mortality as the major force driving the quick evolution of mutation rates. Together, these findings show how organisms balance robustness and evolvability and help explain the prevalence of hypermutation in various settings, ranging from emergence of antibiotic resistance in microbes to cancer relapses upon chemotherapy.DOI: http://dx.doi.org/10.7554/eLife.22939.001

Dynamics of genetic variation in Transcription Factors and its implications for the evolution of regulatory networks in Bacteria

“…For each study, we counted the number of non-synonymous mutations in TFs and TGs relative to the number of corresponding sites. 4 (29,34,35,39) out of 13 ALE studies (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) had a significantly higher number of mutations in TFs than expected whereas none of the MA studies passed the significance test ( Fig. 5) (P One-sided Fisher's exact < 0.05 ).…”

“…First, we identified 17 lab evolution projects with published (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43) information about the experimental design, 4 of which were MA studies (40)(41)(42)(43). For each study, we counted the number of non-synonymous mutations in TFs and TGs relative to the number of corresponding sites.…”

No genome is an island: toward a 21st century agenda for evolution

“…Increased mutation rates observed in starved E. coli populations have been attributed to the induction of hypermutable cell subpopulations . Similarly, ethanol exposure has been reported to induce a transient hypermutable state allowing the acquisition of adaptive mutations …”

“…162 Similarly, ethanol exposure has been reported to induce a transient hypermutable state allowing the acquisition of adaptive mutations. 163 In yeast, studies of starvation-induced mutagenesis are more limited, but one set of reports is particularly notable because the genome changes resemble those observed following interspecific hybridization. In the initial study, cells were tested from cultures starved for a month on spent growth medium, and 70% of cells tested from these starved populations harbored at least one chromosome rearrangement.…”

Irregularities in genetic variation and mutation rates with environmental stresses

“…The effect of additional environmental variables, including other nutritional stresses, was recently characterized and shown to induce variation in mutational outcomes (Maharjan and Ferenci, 2017b;Shewaramani et al, 2017). Mutational variation with temperature (Chu et al, 2018), with reduced growth rate (Maharjan and Ferenci, 2018a), with oxygen radicals (Correa et al, 2018) and with high ethanol (Swings et al, 2017) has been studied, and other examples of mutational patterns changed by environments have been given (Foster et al, 2018). in vivo changes in mutation rate elicited by bile salt stress have also been postulated (Urdaneta et al, 2019).…”