Coevolution with viruses drives the evolution of bacterial mutation rates

Bacteria with greatly elevated mutation rates ( mutators) are frequently found in natural(1-3) and laboratory(4,5) populations, and are often associated with clinical infections(6,7). Although mutators may increase adaptability to novel environmental conditions, they are also prone to the accumulation of deleterious mutations. The long-term maintenance of high bacterial mutation rates is therefore likely to be driven by rapidly changing selection pressures(8-14), in addition to the possible slow transition rate by point mutation from mutators to non- mutators(15). One of the most likely causes of rapidly changing selection pressures is antagonistic coevolution with parasites(16,17). Here we show whether coevolution with viral parasites could drive the evolution of bacterial mutation rates in laboratory populations of the bacterium Pseudomonas fluorescens(18). After fewer than 200 bacterial generations, 25% of the populations coevolving with phages had evolved 10- to 100- fold increases in mutation rates owing to mutations in mismatch-repair genes; no populations evolving in the absence of phages showed any significant change in mutation rate. Furthermore, mutator populations had a higher probability of driving their phage populations extinct, strongly suggesting that mutators have an advantage against phages in the coevolutionary arms race. Given their ubiquity, bacteriophages may play an important role in the evolution of bacterial mutation rates.