Hypermutator emergence in experimental Escherichia coli populations is stress-type dependent

Genotypes exhibiting an increased mutation rate, called hypermutators, can propagate in microbial populations because they can have an advantage due to the higher supply of beneficial mutations needed for adaptation. Although this is a frequently observed phenomenon in natural and laboratory populations, little is known about the influence of parameters such as the degree of maladaptation, stress intensity, and the genetic architecture for adaptation on the emergence of hypermutators. To address this knowledge gap, we measured the emergence of hypermutators over similar to 1,000 generations in experimental Escherichia coli populations exposed to different levels of osmotic or antibiotic stress. Our stress types were chosen based on the assumption that the genetic architecture for adaptation differs between them. Indeed, we show that the size of the genetic basis for adaptation is larger for osmotic stress compared to antibiotic stress. During our experiment, we observed an increased emergence of hypermutators in populations exposed to osmotic stress but not in those exposed to antibiotic stress, indicating that hypermutator emergence rates are stress type dependent. These results support our hypothesis that hypermutator emergence is linked to the size of the genetic basis for adaptation. In addition, we identified other parameters that covaried with stress type (stress level and IS transposition rates) that might have contributed to an increased hypermutator provision and selection. Our results provide a first comparison of hypermutator emergence rates under varying stress conditions and point towards complex interactions of multiple stress-related factors on the evolution of mutation rates.

Automated summary

The emergence of hypermutators is influenced by parameters such as maladaptation, stress intensity, and genetic architecture for adaptation. This study found that the number of hypermutators increased under osmotic stress but not under antibiotic stress in Escherichia coli, indicating a correlation between the size of the genetic basis for adaptation and hypermutator emergence. Other parameters related to stress type were also identified that may contribute to increased hypermutator provision and selection. These results highlight the complex interactions of stress-related factors on mutation rate evolution.