Journal of Genetics

, 78:7 | Cite as

Adaptive mutation inEscherichia coli strain FC40

  • Patricia L. Foster
  • William A. Rosche
Special Section: Stationary-Phase Mutations In Microorganisms


Mutations can arise in static populations of cells that are subjected to nonlethal selective pressure, a phenomenon that has been called ‘adaptive mutation’. This phenomenon has been extensively studied in FC40, a strain ofEscherichia coli that cannot metabolize lactose (Lac) but that reverts to lactose utilization (Lac+) when lactose is its sole energy and carbon source. The adaptive Lac+ mutations arise by two mutational processes: a recombination-dependent process that is highly active on the episome carrying the Lac allele, and an unknown process that affects the whole genome. Most of the Lac+ mutations are due to the first process, which also produces nonselected mutations on the F′ episome. However, about 10% of the Lac+ mutations arise in a subpopulation of cells that experience a period of transient hypermutation. Although minor contributors to any one type of mutation, the hypermutators account for nearly all cases of multiple mutations. The evolutionary implications of these results are: (i) DNA synthesis associated with recombination may be an important source of spontaneous mutation, particularly in cells that are not actively growing; (ii) the efficient mutational mechanism that occurs on the episome could result in the horizontal transfer of new alleles among species that carry and exchange conjugal plasmids; and (iii) a subpopulation of transient hypermutators could be a source of multiple mutations that would allow for rapid adaptive evolution under adverse conditions.


spontaneous mutation directed mutation stationary-phase mutation starvation-induced mutation recombination DNA replication 


  1. Andersson D. I., Slechta E. S. and Roth J. R. 1998 Evidence that gene amplification underlies adaptive mutability of the bacteriallac operon.Science 282, 1133–1135.PubMedCrossRefGoogle Scholar
  2. Boe L. 1990 Mechanism for induction of adaptive mutations inEscherichia coli.Mol. Microbiol. 4, 597–601.PubMedCrossRefGoogle Scholar
  3. Boyd E. F. and Hartl D. L. 1997 Recent horizontal transmission of plasmids between natural populations ofEscherichia coli andSalmonella enterica.J. Bacteriol. 179, 1622–1627.PubMedGoogle Scholar
  4. Boyd E. F., Hill C. S., Rich S. M. and Hartl D. L. 1996 Mosaic structure of plasmids from natural populations ofEscherichia coli.Genetics 143, 1091–1100.PubMedGoogle Scholar
  5. Cairns J. 1998 Mutation and cancer: The antecedents to our studies of adaptive mutation.Genetics 148, 1433–1440.PubMedGoogle Scholar
  6. Cairns J. and Foster P. L. 1991 Adaptive reversion of a frameshift mutation inEscherichia coli.Genetics 128, 695–701.PubMedGoogle Scholar
  7. Cairns J., Overbaugh J. and Miller S. 1988 The origin of mutants.Nature 335, 142–145.PubMedCrossRefGoogle Scholar
  8. Calos M. P. and Miller J. H. 1981 Genetic and sequence analysis of frameshift mutations induced by ICR-191.J. Mol. Biol. 153, 39–66.PubMedCrossRefGoogle Scholar
  9. Carter J. R., Patel D. R. and Porter R. D. 1992 The role oforiT intra-dependent enhanced recombination between mini-F-lac-oriT and lambdaplac5.Genet. Res. 59, 157–165.PubMedGoogle Scholar
  10. Christensen R. B., Christensen J. R. and Lawrence C. W. 1985 Conjugation-dependent enhancement of induced and spontaneous mutation in thelacI gene ofE. coli.Mol. Gen. Genet. 201, 35–37.PubMedCrossRefGoogle Scholar
  11. Demerec M. 1963 Selfer mutants ofSalmonella typhimurium.Genetics 48, 1519–1531.PubMedGoogle Scholar
  12. Escarceller M., Hicks J., Gudmundsson G., Trump G., Touati D., Lovett S., Foster P. L., McEntee K. and Goodman M. F. 1994 Involvement ofEscherichia coli DNA polymerase II in response to oxidative damage and adaptive mutation.J. Bacteriol. 176, 6221–6228.PubMedGoogle Scholar
  13. Firth N., Ippen-Ihler K. and Skurray R. A. 1996 Structure and function of the F factor and mechanism of conjugation. InEscherichia coli and Salmonella: cellular and molecular biology (ed. F. C. Neidhardt, R. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. B. Low, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter and H. E. Umbarger), pp. 2377–2412. American Society of Microbiology, Washington, DC.Google Scholar
  14. Foster P. L. 1993 Adaptive mutation: The uses of adversity.Annu. Rev. Microbiol. 47, 467–504.PubMedCrossRefGoogle Scholar
  15. Foster P. L. 1994 Population dynamics of a Lac strain ofEscherichia coli during selection for lactose utilization.Genetics 138, 253–261.PubMedGoogle Scholar
  16. Foster P. L. 1997 Nonadaptive mutations occur on the F′ episome during adaptive mutation conditions inEscherichia coli.J Bacteriol. 179, 1550–1554.PubMedGoogle Scholar
  17. Foster P. L. 1999 Are adaptive mutations due to a decline in mismatch repair? The evidence is lacking.Mutat. Res. 436, 179–184.PubMedCrossRefGoogle Scholar
  18. Foster P. L. and Cairns J. 1992 Mechanisms of directed mutation.Genetics 131, 783–789.PubMedGoogle Scholar
  19. Foster P. L. and Rosche W. A. 1999 Increased episomal replication accounts for the high rate of adaptive mutation inrecD mutants ofEscherichia coli.Genetics 152, 15–30.PubMedGoogle Scholar
  20. Foster P. L. and Trimarchi J. M. 1994 Adaptive reversion of a frameshift mutation inEscherichia coli by simple base deletions in homopolymeric runs.Science 265, 407–409.PubMedCrossRefGoogle Scholar
  21. Foster P. L. and Trimarchi J. M. 1995a Adaptive reversion of an episomal frameshift mutation inEscherichia coli requires conjugal functions but not actual conjugation.Proc. Natl. Acad. Sci. USA 92, 5487–5490.PubMedCrossRefGoogle Scholar
  22. Foster P. L. and Trimarchi J. M. 1995b Conjugation is not required for adaptive reversion of an episomal frameshift mutation inEscherichia coli.J. Bacteriol. 177, 6670–6671.PubMedGoogle Scholar
  23. Foster P. L., Gudmundsson G., Trimarchi J. M., Cai H. and Goodman M. F. 1995 Proofreading-defective DNA polymerase II increases adaptive mutation inEscherichia coli.Proc. Natl. Acad. Sci. USA 92, 7951–7955.PubMedCrossRefGoogle Scholar
  24. Foster P. L., Trimarchi J. M. and Maurer R. A. 1996 Two enzymes, both of which process recombination intermediates, have opposite effects on adaptive mutation inEscherichia coli.Genetics 142, 25–37.PubMedGoogle Scholar
  25. Frost L. S. and Manchak J. 1998 F phenocopies: characterization of expression of the F transfer region in stationary phase.Microbiology 144, 2579–2587.PubMedCrossRefGoogle Scholar
  26. Galitski T. and Roth J. R. 1995 Evidence that F plasmid transfer replication underlies apparent adaptive mutation.Science 268, 421–423.PubMedCrossRefGoogle Scholar
  27. Hall B. G. 1990 Spontaneous point mutations that occur more often when they are advantageous than when they are neutral.Genetics 126, 5–16.PubMedGoogle Scholar
  28. Harris R. S., Longerich S. and Rosenberg S. M. 1994 Recombination in adaptive mutation.Science 264, 258–260.PubMedCrossRefGoogle Scholar
  29. Harris R. S., Ross K. J. and Rosenberg S. M. 1996 Opposing roles of the Holliday junction processing systems ofEscherichia coli in recombination-dependent adaptive mutation.Genetics 142, 681–691.PubMedGoogle Scholar
  30. Harris R. S., Bull H. J. and Rosenberg S. M. 1997a A direct role for DNA polymerase III in adaptive reversion of a frameshift mutation inEscherichia coli.Mutat. Res. 375, 19–25.PubMedGoogle Scholar
  31. Harris R. S., Feng G., Ross K. J., Sidhu R., Thulin C., Longerich S., Szigety S. K., Winkler M. E. and Rosenberg S. M. 1997b Mismatch repair protein MutL becomes limiting during stationary-phase mutation.Genes Dev. 11, 2426–2437.PubMedCrossRefGoogle Scholar
  32. Holloway B. and Low K. B. 1996 F-prime and R-prime factors. InEscherichia coli and Salmonella: cellular and molecular biology (ed. F. C. Neidhardt, R. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. B. Low, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter and H. E. Umbarger), pp. 2413–2420. American Society of Microbiology, Washington, DC.Google Scholar
  33. Kogoma T. 1997 Stable DNA replication: interplay between DNA replication, homologous recombination, and transcription.Microbiol. Mol. Biol. Rev. 61, 212–238.PubMedGoogle Scholar
  34. Kowalczykowski S. D., Dixon D. A., Eggleston A. K., Lauder S. C. and Rehrauer W. M. 1994 Biochemistry of homologous recombination inEscherichia coli.Microbiol. Rev. 58, 401–465.PubMedGoogle Scholar
  35. Kunz B. A. and Glickman B. W. 1983 The infidelity of conjugal DNA transfer inEscherichia coli.Genetics 105, 489–500.PubMedGoogle Scholar
  36. Kuzminov A. 1995 Collapse and repair of replication forks inEscherichia coli.Mol. Microbiol. 16, 373–384.PubMedCrossRefGoogle Scholar
  37. Marians K. J., Hiasa H., Kim D. R. and McHenry C. S. 1998 Role of the core DNA polymerase III subunits at the replication fork;α is the only subunit required for processive replication.J. Biol. Chem. 273, 2452–2457.PubMedCrossRefGoogle Scholar
  38. Miller J. H. 1985 Mutagenic specificity of ultraviolet light.J. Mol. Biol. 182, 45–65.PubMedCrossRefGoogle Scholar
  39. Modrich P. and Lahue R. 1996 Mismatch repair in replication fidelity, genetic recombination, and cancer biology.Annu. Rev. Biochem. 65, 101–133.PubMedCrossRefGoogle Scholar
  40. Ninio J. 1991 Transient mutators: A semiquantitative analysis of the influence of translation and transcription errors on mutation rates.Genetics 129, 957–962.PubMedGoogle Scholar
  41. Radicella J. P., Park P. U. and Fox M. S. 1995 Adaptive mutation inEscherichia coli: A role for conjugation.Science 268, 418–420.PubMedCrossRefGoogle Scholar
  42. Rangarajan S., Gudmundsson G., Qiu Z., Foster P. L. and Goodman M. F. 1997Escherichia coli DNA polymerase II catalyzes chromosomal and episomal DNA synthesisin vivo.Proc. Natl. Acad. Sci. USA 94, 946–951.PubMedCrossRefGoogle Scholar
  43. Rosche W. A. and Foster P. L. 1999 The role of transient hypermutators in adaptive mutation inEscherichia coli. Proc. Natl. Acad. Sci. USA 96 (in press).Google Scholar
  44. Rosenberg S. M., Longerich S., Gee P. and Harris R. S. 1994 Adaptive mutation by deletions in small mononucleotide repeats.Science 265, 405–407.PubMedCrossRefGoogle Scholar
  45. Roth J. R., Benson N., Galitski T., Haack K., Lawrence J. G. and Miesel L. 1996 Rearrangements of the bacterial chromosome: formation and applications. InEscherichia coli and Salmonella: cellular and molecular biology (ed. F. C. Neidhardt, R. Curtiss III, J. L. Ingraham, E. C. C. Lin, K. B. Low, B. Magasanik, W. S. Reznikoff, M. Riley, M. Schaechter and H. E. Umbarger), pp. 2256–2276. American Society of Microbiology, Washington, DC.Google Scholar
  46. Stahl F. W. 1988 A unicorn in the garden.Nature 335, 112–113.PubMedCrossRefGoogle Scholar
  47. Strathern J. N., Shafer B. K. and McGill C. B. 1995 DNA synthesis errors associated with double-strand-break repair.Genetics 140, 965–972.PubMedGoogle Scholar
  48. Tlsty D. T., Albertini A. M. and Miller J. H. 1984 Gene amplification in thelac region ofE. coli.Cell 37, 217–224.PubMedCrossRefGoogle Scholar
  49. Torkelson J., Harris R. S., Lombardo M.-J., Nagendran J., Thulin C. and Rosenberg S. M. 1997 Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation.EMBO J. 16, 3303–3311.PubMedCrossRefGoogle Scholar
  50. West S. C. 1996 The RuvABC proteins and Holliday junction processing inEscherichia coli.J. Bacteriol. 178, 1237–1241.PubMedGoogle Scholar

Copyright information

© Indian Academy of Sciences 1999

Authors and Affiliations

  1. 1.Department of Environmental HealthBoston University School of Public HealthBostonUSA

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