The mutational landscape of Bacillus subtilis conditional hypermutators shows how proofreading skews DNA polymerase error rates.

Polymerase errors during DNA replication are a major source of point mutations in genomes. The spontaneous mutation rate also depends on the counteracting activity of DNA repair mechanisms, with mutator phenotypes appearing constantly and allowing for periods of rapid evolution in nature and in the laboratory. Here, we use the Gram-positive model bacterium Bacillus subtilis to disentangle the contributions of DNA polymerase initial nucleotide selectivity, DNA polymerase proofreading, and mismatch repair (MMR) to the mutation rate.