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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LeClerc, J. E., Li, B. G., Payne, W. L. & Cebula, T. A. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274, 1208–1211 (1996)
Matic, I. et al. Highly variable mutation rates in commensal and pathogenic Escherichia coli . Science 277, 1833–1834 (1997)
Trong, H. N. G., Prunier, A. L. & Leclercq, R. Hypermutable and fluoroquinolone-resistant clinical isolates of Staphylococcus aureus . Antimicrob. Agents Chemother. 49, 2098–2101 (2005)
Sniegowski, P. D., Gerrish, P. J. & Lenski, R. E. Evolution of high mutation rates in experimental populations of E. coli . Nature 387, 703–705 (1997)
Giraud, A. et al. Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science 291, 2606–2608 (2001)
Oliver, A., Canton, R., Campo, P., Baquero, F. & Blazquez, J. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science 288, 1251–1253 (2000)
Denamur, E. et al. High frequency of mutator strains among human uropathogenic Escherichia coli isolates. J. Bacteriol. 184, 605–609 (2002)
Leigh, E. G. Natural selection and mutability. Am. Nat. 104, 301–305 (1970)
Ishii, K., Matsuda, H., Iwasa, Y. & Sasaki, A. Evolutionarily stable mutation-rate in a periodically changing environment. Genetics 121, 163–174 (1989)
Taddei, F. et al. Role of mutator alleles in adaptive evolution. Nature 387, 700–702 (1997)
Tenaillon, O., Toupance, B., Le Nagard, H., Taddei, F. & Godelle, B. Mutators, population size, adaptive landscape and the adaptation of asexual populations of bacteria. Genetics 152, 485–493 (1999)
Tanaka, M. M., Bergstrom, C. T. & Levin, B. R. The evolution of mutator genes in bacterial populations: the roles of environmental change and timing. Genetics 164, 843–854 (2003)
Palmer, M. E. & Lipsitch, M. The influence of hitchhiking and deleterious mutation upon asexual mutation rates. Genetics 173, 461–472 (2006)
Andre, J. B. & Godelle, B. The evolution of mutation rate in finite asexual populations. Genetics 172, 611–626 (2006)
Denamur, E. et al. Evolutionary implications of the frequent horizontal transfer of mismatch repair genes. Cell 103, 711–721 (2000)
Hamilton, W. D., Axelrod, R. & Tanese, R. Sexual reproduction as an adaptation to resist parasites (a review). Proc. Natl Acad. Sci. USA 87, 3566–3573 (1990)
West, S. A., Lively, C. M. & Read, A. F. A pluralist approach to sex and recombination. J. Evol. Biol. 12, 1003–1012 (1999)
Buckling, A. & Rainey, P. B. Antagonistic coevolution between a bacterium and a bacteriophage. Proc. R. Soc. Lond. B 269, 931–936 (2002)
Mizoguchi, K. et al. Coevolution of bacteriophage PP01 and Escherichia coli O157: H7 in continuous culture. Appl. Environ. Microbiol. 69, 170–176 (2003)
Morgan, A. D., Gandon, S. & Buckling, A. The effect of migration on local adaptation in a coevolving host–parasite system. Nature 437, 253–256 (2005)
Agrawal, A. & Lively, C. M. Infection genetics: gene-for-gene versus matching-alleles models and all points in between. Evol. Ecol. Res. 4, 79–90 (2002)
Rainey, P. B. & Bailey, M. J. Physical and genetic map of the Pseudomonas fluorescens SBW25 chromosome. Mol. Microbiol. 19, 521–533 (1996)
Morgan, A. D. & Buckling, A. Relative number of generations of hosts and parasites does not influence parasite local adaptation in coevolving populations of bacteria and phages. J. Evol. Biol. 19, 1956–1963 (2006)
Luria, S. & Delbruck, M. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28, 491–511 (1943)
Bjedov, I. et al. Stress-induced mutagenesis in bacteria. Science 300, 1404–1409 (2003)
Oliver, A., Levin, B. R., Juan, C., Baquero, F. & Blazquez, J. Hypermutation and the preexistence of antibiotic-resistant Pseudomonas aeruginosa mutants: implications for susceptibility testing and treatment of chronic infections. Antimicrob. Agents Chemother. 48, 4226–4233 (2004)
Oliver, A., Baquero, F. & Blazquez, J. The mismatch repair system (mutS, mutL and uvrD genes) in Pseudomonas aeruginosa: molecular characterization of naturally occurring mutants. Mol. Microbiol. 43, 1641–1650 (2002)
de Visser, J., Zeyl, C. W., Gerrish, P. J., Blanchard, J. L. & Lenski, R. E. Diminishing returns from mutation supply rate in asexual populations. Science 283, 404–406 (1999)
Chao, L. & Cox, E. C. Competition between high and low mutating strains of Escherichia coli . Evolution Int. J. Org. Evolution 37, 125–134 (1983)
Rosche, W. A. & Foster, P. L. Determining mutation rates in bacterial populations. Methods 20, 4–17 (2000)
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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Pal, C., Maciá, M., Oliver, A. et al. Coevolution with viruses drives the evolution of bacterial mutation rates. Nature 450, 1079–1081 (2007). https://doi.org/10.1038/nature06350
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