Escherichia coli mutation rates and spectra with combinations of environmental limitations

Micro-organisms often face multiple stresses in natural habitats. Individual stresses are well known to influence mutation rates and the spectra of mutational types, but the extent to which multiple stresses affect the genetic variation in populations is unknown. Here we investigate pair-wise combinations of nutritional stresses in Escherichia coli to determine their effect on mutation rates and mutational types. Environmental interactions modified both the rate and spectrum of mutations in double-limited environments, but the effects were not additive or synergistic relative to single stresses. Generally, bacteria in the mixed environments behaved as if one of the two single-stress stimuli was more dominant and the genetic variation seen with every dual limitation was intermediate between known patterns with individual stresses. The composition of mutational types with double stresses was also intermediate between individual stress patterns. At least with mutations, the single stressor results available are reasonable indicators of stress-induced genetic variation in multifaceted natural habitats. With the influence of 11 conditions available on mutational patterns, we can now also see the clustering of mutational types as a function of these environments.