Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2002 Oct;162(2):557–566. doi: 10.1093/genetics/162.2.557

Fitness evolution and the rise of mutator alleles in experimental Escherichia coli populations.

Aaron C Shaver 1, Peter G Dombrowski 1, Joseph Y Sweeney 1, Tania Treis 1, Renata M Zappala 1, Paul D Sniegowski 1
PMCID: PMC1462288  PMID: 12399371

Abstract

We studied the evolution of high mutation rates and the evolution of fitness in three experimental populations of Escherichia coli adapting to a glucose-limited environment. We identified the mutations responsible for the high mutation rates and show that their rate of substitution in all three populations was too rapid to be accounted for simply by genetic drift. In two of the populations, large gains in fitness relative to the ancestor occurred as the mutator alleles rose to fixation, strongly supporting the conclusion that mutator alleles fixed by hitchhiking with beneficial mutations at other loci. In one population, no significant gain in fitness relative to the ancestor occurred in the population as a whole while the mutator allele rose to fixation, but a substantial and significant gain in fitness occurred in the mutator subpopulation as the mutator neared fixation. The spread of the mutator allele from rarity to fixation took >1000 generations in each population. We show that simultaneous adaptive gains in both the mutator and wild-type subpopulations (clonal interference) retarded the mutator fixation in at least one of the populations. We found little evidence that the evolution of high mutation rates accelerated adaptation in these populations.

Full Text

The Full Text of this article is available as a PDF (122.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arjan J. A., Visser M., Zeyl C. W., Gerrish P. J., Blanchard J. L., Lenski R. E. Diminishing returns from mutation supply rate in asexual populations. Science. 1999 Jan 15;283(5400):404–406. doi: 10.1126/science.283.5400.404. [DOI] [PubMed] [Google Scholar]
  2. Ban C., Junop M., Yang W. Transformation of MutL by ATP binding and hydrolysis: a switch in DNA mismatch repair. Cell. 1999 Apr 2;97(1):85–97. doi: 10.1016/s0092-8674(00)80717-5. [DOI] [PubMed] [Google Scholar]
  3. Ban C., Yang W. Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis. Cell. 1998 Nov 13;95(4):541–552. doi: 10.1016/s0092-8674(00)81621-9. [DOI] [PubMed] [Google Scholar]
  4. Blattner F. R., Plunkett G., 3rd, Bloch C. A., Perna N. T., Burland V., Riley M., Collado-Vides J., Glasner J. D., Rode C. K., Mayhew G. F. The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453–1462. doi: 10.1126/science.277.5331.1453. [DOI] [PubMed] [Google Scholar]
  5. Boe L., Danielsen M., Knudsen S., Petersen J. B., Maymann J., Jensen P. R. The frequency of mutators in populations of Escherichia coli. Mutat Res. 2000 Mar 14;448(1):47–55. doi: 10.1016/s0027-5107(99)00239-0. [DOI] [PubMed] [Google Scholar]
  6. Cooper V. S., Lenski R. E. The population genetics of ecological specialization in evolving Escherichia coli populations. Nature. 2000 Oct 12;407(6805):736–739. doi: 10.1038/35037572. [DOI] [PubMed] [Google Scholar]
  7. Gerrish P. J., Lenski R. E. The fate of competing beneficial mutations in an asexual population. Genetica. 1998;102-103(1-6):127–144. [PubMed] [Google Scholar]
  8. Giraud A., Matic I., Tenaillon O., Clara A., Radman M., Fons M., Taddei F. Costs and benefits of high mutation rates: adaptive evolution of bacteria in the mouse gut. Science. 2001 Mar 30;291(5513):2606–2608. doi: 10.1126/science.1056421. [DOI] [PubMed] [Google Scholar]
  9. Gross M. D., Siegel E. C. Incidence of mutator strains in Escherichia coli and coliforms in nature. Mutat Res. 1981 Mar;91(2):107–110. doi: 10.1016/0165-7992(81)90081-6. [DOI] [PubMed] [Google Scholar]
  10. Hall M. C., Jordan J. R., Matson S. W. Evidence for a physical interaction between the Escherichia coli methyl-directed mismatch repair proteins MutL and UvrD. EMBO J. 1998 Mar 2;17(5):1535–1541. doi: 10.1093/emboj/17.5.1535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Johnson T. Beneficial mutations, hitchhiking and the evolution of mutation rates in sexual populations. Genetics. 1999 Apr;151(4):1621–1631. doi: 10.1093/genetics/151.4.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kibota T. T., Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. doi: 10.1038/381694a0. [DOI] [PubMed] [Google Scholar]
  13. Kleckner N., Bender J., Gottesman S. Uses of transposons with emphasis on Tn10. Methods Enzymol. 1991;204:139–180. doi: 10.1016/0076-6879(91)04009-d. [DOI] [PubMed] [Google Scholar]
  14. LEDERBERG J., ZINDER N. Concentration of biochemical mutants of bacteria with penicillin. J Am Chem Soc. 1948 Dec;70(12):4267–4267. doi: 10.1021/ja01192a521. [DOI] [PubMed] [Google Scholar]
  15. Lederberg S. Genetics of host-controlled restriction and modification of deoxyribonucleic acid in Escherichia coli. J Bacteriol. 1966 Mar;91(3):1029–1036. doi: 10.1128/jb.91.3.1029-1036.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lenski R. E., Mongold J. A., Sniegowski P. D., Travisano M., Vasi F., Gerrish P. J., Schmidt T. M. Evolution of competitive fitness in experimental populations of E. coli: what makes one genotype a better competitor than another? Antonie Van Leeuwenhoek. 1998 Jan;73(1):35–47. doi: 10.1023/a:1000675521611. [DOI] [PubMed] [Google Scholar]
  17. Lenski R. E., Travisano M. Dynamics of adaptation and diversification: a 10,000-generation experiment with bacterial populations. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6808–6814. doi: 10.1073/pnas.91.15.6808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Liberman U., Feldman M. W. Modifiers of mutation rate: a general reduction principle. Theor Popul Biol. 1986 Aug;30(1):125–142. doi: 10.1016/0040-5809(86)90028-6. [DOI] [PubMed] [Google Scholar]
  19. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matic I., Radman M., Taddei F., Picard B., Doit C., Bingen E., Denamur E., Elion J. Highly variable mutation rates in commensal and pathogenic Escherichia coli. Science. 1997 Sep 19;277(5333):1833–1834. doi: 10.1126/science.277.5333.1833. [DOI] [PubMed] [Google Scholar]
  21. Notley-McRobb L., Ferenci T. Experimental analysis of molecular events during mutational periodic selections in bacterial evolution. Genetics. 2000 Dec;156(4):1493–1501. doi: 10.1093/genetics/156.4.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Notley-McRobb Lucinda, Pinto Rachel, Seeto Shona, Ferenci Thomas. Regulation of mutY and nature of mutator mutations in Escherichia coli populations under nutrient limitation. J Bacteriol. 2002 Feb;184(3):739–745. doi: 10.1128/JB.184.3.739-745.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Notley-McRobb Lucinda, Pinto Rachel, Seeto Shona, Ferenci Thomas. Regulation of mutY and nature of mutator mutations in Escherichia coli populations under nutrient limitation. J Bacteriol. 2002 Feb;184(3):739–745. doi: 10.1128/JB.184.3.739-745.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oliver A., Cantón R., Campo P., Baquero F., Blázquez J. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science. 2000 May 19;288(5469):1251–1254. doi: 10.1126/science.288.5469.1251. [DOI] [PubMed] [Google Scholar]
  25. Painter P. R. Clone selection and the mutation rate. Theor Popul Biol. 1975 Aug;8(1):74–80. doi: 10.1016/0040-5809(75)90040-4. [DOI] [PubMed] [Google Scholar]
  26. Painter P. R. Mutator genes and selection for the mutation rate in bacteria. Genetics. 1975 Apr;79(4):649–660. doi: 10.1093/genetics/79.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Peck J. R. A ruby in the rubbish: beneficial mutations, deleterious mutations and the evolution of sex. Genetics. 1994 Jun;137(2):597–606. doi: 10.1093/genetics/137.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Radman M., Matic I., Taddei F. Evolution of evolvability. Ann N Y Acad Sci. 1999 May 18;870:146–155. doi: 10.1111/j.1749-6632.1999.tb08874.x. [DOI] [PubMed] [Google Scholar]
  29. Rice W. R., Chippindale A. K. Sexual recombination and the power of natural selection. Science. 2001 Oct 19;294(5542):555–559. doi: 10.1126/science.1061380. [DOI] [PubMed] [Google Scholar]
  30. Siegel E. C. Ultraviolet-sensitive mutator strain of Escherichia coli K-12. J Bacteriol. 1973 Jan;113(1):145–160. doi: 10.1128/jb.113.1.145-160.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sniegowski P. D., Gerrish P. J., Johnson T., Shaver A. The evolution of mutation rates: separating causes from consequences. Bioessays. 2000 Dec;22(12):1057–1066. doi: 10.1002/1521-1878(200012)22:12<1057::AID-BIES3>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  32. Sniegowski P. D., Gerrish P. J., Lenski R. E. Evolution of high mutation rates in experimental populations of E. coli. Nature. 1997 Jun 12;387(6634):703–705. doi: 10.1038/42701. [DOI] [PubMed] [Google Scholar]
  33. Spampinato C., Modrich P. The MutL ATPase is required for mismatch repair. J Biol Chem. 2000 Mar 31;275(13):9863–9869. doi: 10.1074/jbc.275.13.9863. [DOI] [PubMed] [Google Scholar]
  34. Taddei F., Radman M., Maynard-Smith J., Toupance B., Gouyon P. H., Godelle B. Role of mutator alleles in adaptive evolution. Nature. 1997 Jun 12;387(6634):700–702. doi: 10.1038/42696. [DOI] [PubMed] [Google Scholar]
  35. Tenaillon O., Le Nagard H., Godelle B., Taddei F. Mutators and sex in bacteria: conflict between adaptive strategies. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10465–10470. doi: 10.1073/pnas.180063397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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. 1999 Jun;152(2):485–493. doi: 10.1093/genetics/152.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tran P. T., Liskay R. M. Functional studies on the candidate ATPase domains of Saccharomyces cerevisiae MutLalpha. Mol Cell Biol. 2000 Sep;20(17):6390–6398. doi: 10.1128/mcb.20.17.6390-6398.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Tröbner W., Piechocki R. Competition between isogenic mutS and mut+ populations of Escherichia coli K12 in continuously growing cultures. Mol Gen Genet. 1984;198(2):175–176. doi: 10.1007/BF00328719. [DOI] [PubMed] [Google Scholar]
  39. Yamaguchi M., Dao V., Modrich P. MutS and MutL activate DNA helicase II in a mismatch-dependent manner. J Biol Chem. 1998 Apr 10;273(15):9197–9201. doi: 10.1074/jbc.273.15.9197. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES