Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Role of mutator alleles in adaptive evolution

Abstract

Because most newly arising mutations are neutral or deleterious, it has been argued1,2,3 that the mutation rate has evolved to be as low as possible, limited only by the cost of error-avoidance and error-correction mechanisms. But up to one per cent of natural bacterial isolates are ‘mutator’ clones that have high mutation rates4,5,6. We consider here whether high mutation rates might playan important role in adaptive evolution. Models of large, asexual, clonal populations adapting to a new environment show that strong mutator genes (such as those that increase mutation rates by 1,000-fold) can accelerate adaptation, even if the mutator gene remains at a very low frequency (for example, 10−5). Less potent mutators (10 to 100-fold increase) can become fixed in a fraction of finite populations. The parameters of the model have been set to values typical for Escherichia coli cultures, which behave in a manner similar to the model in long-term adaptation experiments7.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Mutators as a fast track to generate adaptive mutations.
Figure 2: Mutators speed up evolution even when they are not fixed in infinite populations.
Figure 3: Intermediate mutators can be fixed during adaptation of finite size populations (10-fold mutators are shown).

Similar content being viewed by others

References

  1. Drake, J. W. Aconstant rate of spontaneous mutation in DNA-based microbes. Proc. Natl Acad. Sci. USA 88, 7160–7164 (1991).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kimura, M. On the evolutionary adjustment of spontaneous mutation rates. Genet. Res. 9, 23–34 (1967).

    Article  ADS  Google Scholar 

  3. Leigh, E. G. The evolution of mutation rates. Genetics 73, 1–18 (1973).

    ADS  MathSciNet  Google Scholar 

  4. Jyssum, K. Observation of two types of genetic instability in Escherichia coli. Acta Pathol. Microbiol. Immunol. Scand. 48, 113–120 (1960).

    Article  CAS  Google Scholar 

  5. Gross, M. D. & Siegel, E. C. Incidence of mutator strains in Escherichia coli and coliforms in nature. Mutat. Res. 91, 107–110 (1981).

    Article  CAS  PubMed  Google Scholar 

  6. LeClerc, J. E., Li, B., Payne, W. L. & Cebula, T. A. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 274, 1208–1211 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. 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).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Liberman, U. & Feldman, M. W. Modifiers of mutation rate: a general reduction principle. Theor. Pop. Biol. 30, 125–142 (1986).

    Article  MathSciNet  CAS  Google Scholar 

  9. Leigh, E. G. Natural selection and mutability. Am. Nat. 104, 301–305 (1970).

    Article  Google Scholar 

  10. Ishii, K., Matsuda, H., Iwasa, Y. & Sasaki, A. Evolutionary stable mutation rate in a periodically changing environment. Genetics 121, 163–174 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Van Valen, L. Anew evolutionary law. Evol. Theory 1, 1–30 (1973).

    Google Scholar 

  12. Moxon, E. R., Rainey, P. B., Nowak, M. A. & Lenski, R. E. Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr. Biol. 4, 24–33 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Haraguchi, Y. & Sasaki, A. Host-parasite arms race in mutation modifications: indefinite escalation despite a heavy load. J. Theor. Biol. 183, 121–137 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Mao, E. F., Lane, L., Lee, J. & Miller, J. H. Proliferation of mutators in a cell population. J. Bacteriol. 179, 417–422 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chao, L. & Cox, E. C. Competition between high and low mutating strains of Escherichia coli. Evolution 37, 125–134 (1983).

    Article  PubMed  Google Scholar 

  16. Tröbner, W. & Piechocki, R. Competition growth between Escherichia coli mutL and mut+ in continuously growing cultures. Z. Allg. Mikrobiol. 21, 347–349 (1981).

    Article  PubMed  Google Scholar 

  17. Tröbner, W. & Piechocki, R. Competition between isogenic mutS and mut+populations of Escherichia coli K12 in continuously growing cultures. Mol. Gen. Genet. 198, 175–176 (1984).

    Article  PubMed  Google Scholar 

  18. Tröbner, W. & Piechocki, R. Selective advantage of polA1 mutator over polA+strains of Escherichia coli in a chemostat. Naturwissenschaften 72, 377–378 (1985).

    Article  ADS  PubMed  Google Scholar 

  19. Chao, L., Vargas, C., Spear, B. B. & Cox, E. C. Transposable elements as mutator genes in evolution. Nature 303, 633–635 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Ninio, J. Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. Genetics 129, 957–962 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Lenski, R. E., Rose, M. R., Simpson, S. C. & Tadler, S. C. Long-term experimental evolution in E. coli. I, Adaptation and divergence during 2000 generations. Am. Nat. 138, 1315–1341 (1991).

    Article  Google Scholar 

  22. Lenski, R. E. & Travisano, M. Dynamics of adaptation and diversification: a 10,000-generation experiment with bacterial populations. Proc. Natl Acad. Sci. USA 91, 6808–6814 (1994).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hartl, D. L. & Dykhuizen, D. E. The population genetics of Escherichia coli. Annu. Rev. Genet. 18, 31–68 (1984).

    Article  CAS  PubMed  Google Scholar 

  24. Maynard-Smith, J., Smith, N. H., O'Rourke, M. & Spratt, B. G. How clonal are bacteria? Proc. Natl Acad. Sci. USA 90, 4384–4388 (1993).

    Article  ADS  Google Scholar 

  25. Matic, I., Taddei, F. & Radman, M. Genetic barriers among bacteria. Trends Microbiol. 4, 69–73 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Peck, J. R. Aruby in the rubbish: beneficial mutations, deleterious mutations and the evolution of sex. Genetics 137, 597–606 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. David, J. L., Savy, Y. & Brabant, P. Outcrossing and selfing evolution in populations under directional selection. Heredity 71, 642–651 (1993).

    Article  Google Scholar 

  28. Tomlinson, I. P. M., Novelli, M. R. & Bodmer, W. F. The mutation rate and cancer. Proc. Natl Acad. Sci. USA 93, 14800–14803 (1996).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  29. Magnasco, M. O. & Thaler, D. S. Changing the pace of evolution. Phys. Lett. A 221, 287–292 (1996).

    Article  ADS  MathSciNet  Google Scholar 

  30. Taddei, F., Vulic, M., Radman, M. & Matic, I. in Environmental Stress, Adaptation and Evolution (eds Bijlsma, K. & Loeschcke, V.) (Birkhäuser, Basel, in the press).

Download references

Acknowledgements

Most of the simulations used the SP2 computer, at the Centre de Ressources Informatiques de l'Université de Paris-Sud (Orsay). We are grateful to M.-P. Donsimoni for providing us with a favourable environment and to J. Shykoff and N. Smith for eliminating deleterious style and generating favourable comments. This work has been funded by ‘Bureau des Ressources Génétiques, Ministère de l'Environnement, Association de la Recherche contre le Cancer, Actions Concertées Coordonnées-Sciences du Vivant du Ministère de l'Enseignement Supérieur et de la Recherche and Groupement de Recherche et d'Etudes sur les Génomes’.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to F. Taddei or B. Godelle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taddei, F., Radman, M., Maynard-Smith, J. et al. Role of mutator alleles in adaptive evolution. Nature 387, 700–702 (1997). https://doi.org/10.1038/42696

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/42696

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing