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Coevolution with viruses drives the evolution of bacterial mutation rates


Bacteria with greatly elevated mutation rates (mutators) are frequently found in natural1,2,3 and laboratory4,5 populations, and are often associated with clinical infections6,7. 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 pressures8,9,10,11,12,13,14, in addition to the possible slow transition rate by point mutation from mutators to non-mutators15. One of the most likely causes of rapidly changing selection pressures is antagonistic coevolution with parasites16,17. Here we show whether coevolution with viral parasites could drive the evolution of bacterial mutation rates in laboratory populations of the bacterium Pseudomonas fluorescens18. 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.

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Figure 1: Simulation results (see Supplementary Information ).
Figure 2: Relative mutation rates.
Figure 3: The frequency of coevolving populations of bacteria evolving elevated mutation rates and driving phages extinct, through time.
Figure 4: Competition experiments between wild-type and isogenic mutator.


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We thank A. Spiers for providing sequence data. This work was funded by NERC UK (A.B. and C.P.); the Royal Society (A.B.); EMBO and Hungarian Research Grant (C.P.); Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Spanish Network for the Research in Infectious Diseases (A.O. and M.D.M.).

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Correspondence to Csaba Pal or Angus Buckling.

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The file contains Supplementary Methods, Supplementary Tables 1-4 and Supplementary Figures 1-3 with Legends. (PDF 429 kb)

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Pal, C., Maciá, M., Oliver, A. et al. Coevolution with viruses drives the evolution of bacterial mutation rates. Nature 450, 1079–1081 (2007).

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