Genomic confirmation of nutrient-dependent mutability of mutators in Escherichia coli

Mutators with increased mutation rates are prevalent in various environments and have important roles in accelerating adaptive evolution. Previous studies on mutator strains of microorganisms have shown that some mutators have constant mutation rates, whereas others exhibit switchable mutation rates depending on nutritional conditions. This suggests that the contributions of mutators on evolution vary with fluctuating nutritional conditions. However, such conditional mutability has been unclear at the genomic level. In addition, it is still unknown why mutation rates change with nutritional condition. Here, we used two mutator strains of Escherichia coli to explore the nutrient dependence of mutation rates at the genomic level. These strains were transferred repeatedly under different nutritional conditions for hundreds of generations to accumulate mutations. Whole-genome sequencing of the offspring showed that the nutrient dependence of the mutation rates was pervasive at the genomic scale. Neutrality in the mutation accumulation processes and constancy in the mutational bias suggested that nutrient dependence was not derived from conditional selective purges or from shifts of mutational bias. Some mutators could simply switch their mutation rates for both transitions and transversions in response to nutritional shifts.