Genome-wide analysis of mutagenesis bias and context sensitivity of N-methyl-N′-nitro-N-nitrosoguanidine (NTG)

We have analyzed the mutation spectrum of N-methyl-N′-nitro-N-nitrosoguanidine (NTG) from a set of 4099 mutations identified from whole-genome sequencing of 32 E. coli strains mutagenized with NTG. These data permit precise measurement of NTG's bias for G/C to A/T transitions (96.6% of all mutations) and also show that NTG mutagenesis is strongly sensitive to context, favoring guanine residues preceded by purines by five-fold over those preceded by pyrimidines. These data give confident estimates for the GC bias and transition/transversion ratios of NTG mutagenesis, which could not be estimated confidently from previous, much smaller datasets.

► Larger data set permits a genome-wide estimate of mutation spectrum due to NTG-induced mutagenesis. ► Smaller confidence intervals for the GC bias and transition/transversion ratios of NTG mutagenesis are given. ► NTG mutagenesis is shown to be sensitive to nucleotide context. ► Context sensitivity is measured in terms of conditional probabilities, which are not affected by variations in GC content.