Environmental and genetic influence on rate and spectrum of spontaneous mutations inEscherichia coli

Abstract Spontaneous mutations are the ultimate source of novel genetic variation on which evolution operates. While mutation rate is commonly described as a single parameter in evolutionary models, it is increasingly evident that mutation rates vary due to changes in the rate of distinct nucleotide substitutions. Moreover, the rates of these substitutions can be influenced by genomic background and environmental conditions. Here we characterised the spectrum of spontaneous mutations in Escherichia coli grown in low and high glucose environments, conditions known to affect the rate of spontaneous mutation. We compared changes in the mutational spectrum in a wild-type strain and a strain where the response of mutation rate to glucose is greatly diminished (a deletant for luxS , a gene involved in both quorum sensing and intracellular methylation regulation). We find an increase in AT>GC transitions in the low glucose environment, suggesting that processes relating to the production or repair of this mutation could drive the response of mutation rate to glucose concentration. Interestingly, this increase in AT>GC transitions is maintained by the non-responsive Δ luxS deletant. Instead, an elevated rate of GC>TA transversions in both glucose environments leads to a net non-responsiveness of overall mutation rate. Our results show how relatively subtle changes, such as the concentration of a carbon substrate or loss of a regulatory gene, can substantially influence the amount and nature of genetic variation available to selection.