Mutational Signatures in Wild Type Escherichia coli Strains Reveal Predominance of DNA Polymerase Errors

Abstract

While mutational processes operating in the Escherichia coli genome have been revealed by multiple laboratory experiments, the contribution of these processes to accumulation of bacterial polymorphism and evolution in natural environments is unknown. To address this question, we reconstruct signatures of distinct mutational processes from experimental data on E. coli hypermutators, and ask how these processes contribute to differences between naturally occurring E. coli strains. We show that both mutations accumulated in the course of evolution of wild-type strains in nature and in the lab-grown nonmutator laboratory strains are explained predominantly by the low fidelity of DNA polymerases II and III. By contrast, contributions specific to disruption of DNA repair systems cannot be detected, suggesting that temporary accelerations of mutagenesis associated with such disruptions are unimportant for within-species evolution. These observations demonstrate that accumulation of diversity in bacterial strains in nature is predominantly associated with errors of DNA polymerases.

Keywords: Escherichia; mutation bias; mutation rate; mutation spectrum; mutational signatures.

Fig. 1.

Reconstruction and validation of mutational signatures from the mutator data. a) Cosine similarity matrix between 3-letter mutational profiles for various mutator strains. b) Signatures of mutational processes reconstructed from the mutator strains (see also supplementary fig. S4, Supplementary Material online). c) Similarity between the original and reconstructed profiles for the mutator strains. d) Signatures of mutational processes are correctly assigned to the mutator strains. The size of the circle represents the mean contribution of the mutational signature in the sample, and the color of the circle represents the percentage of bootstrap replicates where this signature was observed.

Fig. 2.

Phylogenetic tree of 522 complete E. coli genomes. The maximum likelihood tree was reconstructed from the concatenated alignment of universal single-copy orthologous genes (see Material and Methods). The four analyzed clades, A , B1, B2, and E are indicated with gray arcs. Leaves for which the phylogroup is indicated in metadata are colored accordingly. Black leaves mean that no phylogroup information is available.

Fig. 3.

Contribution of mutational signatures to the evolution of intergenic regions in E. coli natural and in nonmutator laboratory strains. a) Mutational profile for nonmutator strains and clade B1. (Profiles for all clades are shown in supplementary fig. S6, Supplementary Material online.) b) Cosine similarity between the original mutational profiles and the reconstructed profiles. The horizontal line is at 0.85. c) Relative contribution of each signature to the reconstructed profile. Each dot is the value obtained in one bootstrap replicate. Dots are colored by the data type as in (b).