Skip to main content
PMC home page
Journal of Bacteriology logoLink to Journal of Bacteriology
. 1997 Jan;179(2):417–422. doi: 10.1128/jb.179.2.417-422.1997

Proliferation of mutators in A cell population.

E F Mao 1, L Lane 1, J Lee 1, J H Miller 1
PMCID: PMC178711  PMID: 8990293

Abstract

A Lac- strain of Escherichia coli that reverts by the addition of a G to a G-G-G-G-G-G sequence was used to study the proliferation of mutators in a bacterial culture. Selection for the Lac+ phenotype, which is greatly stimulated in mismatch repair-deficient strains, results in an increase in the percentage of mutators in the selected population from less than 1 per 100,000 cells to 1 per 200 cells. All the mutators detected were deficient in the mismatch repair system. Mutagenesis results in a similar increase in the percentage of mutators. Mutagenesis combined with a single selection can result in a population of more than 50% mutators when a sample of several thousand cells is grown out and selected. Mutagenesis combined with two or more successive selections can generate a population that is 100% mutator. These experiments are discussed in relation to ideas that an early step in carcinogenesis is the creation of a mutator phenotype.

Full Text

The Full Text of this article is available as a PDF (217.6 KB).

Selected References

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

  1. Bronner C. E., Baker S. M., Morrison P. T., Warren G., Smith L. G., Lescoe M. K., Kane M., Earabino C., Lipford J., Lindblom A. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature. 1994 Mar 17;368(6468):258–261. doi: 10.1038/368258a0. [DOI] [PubMed] [Google Scholar]
  2. Cox E. C. Bacterial mutator genes and the control of spontaneous mutation. Annu Rev Genet. 1976;10:135–156. doi: 10.1146/annurev.ge.10.120176.001031. [DOI] [PubMed] [Google Scholar]
  3. Cox E. C., Gibson T. C. Selection for high mutation rates in chemostats. Genetics. 1974 Jun;77(2):169–184. doi: 10.1093/genetics/77.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cupples C. G., Cabrera M., Cruz C., Miller J. H. A set of lacZ mutations in Escherichia coli that allow rapid detection of specific frameshift mutations. Genetics. 1990 Jun;125(2):275–280. doi: 10.1093/genetics/125.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Degnen G. E., Cox E. C. Conditional mutator gene in Escherichia coli: isolation, mapping, and effector studies. J Bacteriol. 1974 Feb;117(2):477–487. doi: 10.1128/jb.117.2.477-487.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FOULDS L. The experimental study of tumor progression: a review. Cancer Res. 1954 Jun;14(5):327–339. [PubMed] [Google Scholar]
  7. Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
  8. Fowler R. G., Degnen G. E., Cox E. C. Mutational specificity of a conditional Escherichia coli mutator, mutD5. Mol Gen Genet. 1974;133(3):179–191. doi: 10.1007/BF00267667. [DOI] [PubMed] [Google Scholar]
  9. Geiser A. G., Burmester J. K., Webbink R., Roberts A. B., Sporn M. B. Inhibition of growth by transforming growth factor-beta following fusion of two nonresponsive human carcinoma cell lines. Implication of the type II receptor in growth inhibitory responses. J Biol Chem. 1992 Feb 5;267(4):2588–2593. [PubMed] [Google Scholar]
  10. Gibson T. C., Scheppe M. L., Cox E. C. Fitness of an Escherichia coli mutator gene. Science. 1970 Aug 14;169(3946):686–688. doi: 10.1126/science.169.3946.686. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Helling R. B. Selection of a mutant of Escherichia coli which has high mutation rates. J Bacteriol. 1968 Oct;96(4):975–980. doi: 10.1128/jb.96.4.975-980.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoess R. H., Herman R. K. Isolation and characterization of mutator strains of Escherichia coli K-12. J Bacteriol. 1975 May;122(2):474–484. doi: 10.1128/jb.122.2.474-484.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. JYSSUM K. Observations on two types of genetic instability in Escherichia coli. Acta Pathol Microbiol Scand. 1960;48:113–120. doi: 10.1111/j.1699-0463.1960.tb04747.x. [DOI] [PubMed] [Google Scholar]
  15. Knudson A. G. Antioncogenes and human cancer. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10914–10921. doi: 10.1073/pnas.90.23.10914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leach F. S., Nicolaides N. C., Papadopoulos N., Liu B., Jen J., Parsons R., Peltomäki P., Sistonen P., Aaltonen L. A., Nyström-Lahti M. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993 Dec 17;75(6):1215–1225. doi: 10.1016/0092-8674(93)90330-s. [DOI] [PubMed] [Google Scholar]
  17. Liberfarb R. M., Bryson V. Isolation, characterization, and genetic analysis of mutator genes in Escherichia coli B and K-12. J Bacteriol. 1970 Oct;104(1):363–375. doi: 10.1128/jb.104.1.363-375.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lin H. Y., Wang X. F., Ng-Eaton E., Weinberg R. A., Lodish H. F. Expression cloning of the TGF-beta type II receptor, a functional transmembrane serine/threonine kinase. Cell. 1992 Feb 21;68(4):775–785. doi: 10.1016/0092-8674(92)90152-3. [DOI] [PubMed] [Google Scholar]
  19. Loeb L. A. Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res. 1994 Oct 1;54(19):5059–5063. [PubMed] [Google Scholar]
  20. Loeb L. A. Mutator phenotype may be required for multistage carcinogenesis. Cancer Res. 1991 Jun 15;51(12):3075–3079. [PubMed] [Google Scholar]
  21. Markowitz S., Wang J., Myeroff L., Parsons R., Sun L., Lutterbaugh J., Fan R. S., Zborowska E., Kinzler K. W., Vogelstein B. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science. 1995 Jun 2;268(5215):1336–1338. doi: 10.1126/science.7761852. [DOI] [PubMed] [Google Scholar]
  22. Marx J. Learning how to suppress cancer. Science. 1993 Sep 10;261(5127):1385–1387. doi: 10.1126/science.8367721. [DOI] [PubMed] [Google Scholar]
  23. Miller J. H. Spontaneous mutators in bacteria: insights into pathways of mutagenesis and repair. Annu Rev Microbiol. 1996;50:625–643. doi: 10.1146/annurev.micro.50.1.625. [DOI] [PubMed] [Google Scholar]
  24. Miyake T. Mutator Factor in Salmonella Typhimurium. Genetics. 1960 Jan;45(1):11–14. doi: 10.1093/genetics/45.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Moustakas A., Lin H. Y., Henis Y. I., Plamondon J., O'Connor-McCourt M. D., Lodish H. F. The transforming growth factor beta receptors types I, II, and III form hetero-oligomeric complexes in the presence of ligand. J Biol Chem. 1993 Oct 25;268(30):22215–22218. [PubMed] [Google Scholar]
  26. Nestmann E. R., Hill R. F. Population changes in continuously growing mutator cultures of Escherichia coli. Genetics. 1973 Apr;73(Suppl):41–44. [PubMed] [Google Scholar]
  27. Nghiem Y., Cabrera M., Cupples C. G., Miller J. H. The mutY gene: a mutator locus in Escherichia coli that generates G.C----T.A transversions. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2709–2713. doi: 10.1073/pnas.85.8.2709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ninio J. Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates. Genetics. 1991 Nov;129(3):957–962. doi: 10.1093/genetics/129.3.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nowell P. C. The clonal evolution of tumor cell populations. Science. 1976 Oct 1;194(4260):23–28. doi: 10.1126/science.959840. [DOI] [PubMed] [Google Scholar]
  30. Papadopoulos N., Nicolaides N. C., Wei Y. F., Ruben S. M., Carter K. C., Rosen C. A., Haseltine W. A., Fleischmann R. D., Fraser C. M., Adams M. D. Mutation of a mutL homolog in hereditary colon cancer. Science. 1994 Mar 18;263(5153):1625–1629. doi: 10.1126/science.8128251. [DOI] [PubMed] [Google Scholar]
  31. Park K., Kim S. J., Bang Y. J., Park J. G., Kim N. K., Roberts A. B., Sporn M. B. Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8772–8776. doi: 10.1073/pnas.91.19.8772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Siegel E. C., Bryson V. Mutator gene of Escherichia coli B. J Bacteriol. 1967 Jul;94(1):38–47. doi: 10.1128/jb.94.1.38-47.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Treffers H. P., Spinelli V., Belser N. O. A Factor (or Mutator Gene) Influencing Mutation Rates in Escherichia Coli. Proc Natl Acad Sci U S A. 1954 Nov;40(11):1064–1071. doi: 10.1073/pnas.40.11.1064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wrana J. L., Attisano L., Cárcamo J., Zentella A., Doody J., Laiho M., Wang X. F., Massagué J. TGF beta signals through a heteromeric protein kinase receptor complex. Cell. 1992 Dec 11;71(6):1003–1014. doi: 10.1016/0092-8674(92)90395-s. [DOI] [PubMed] [Google Scholar]
  35. Wu S. P., Theodorescu D., Kerbel R. S., Willson J. K., Mulder K. M., Humphrey L. E., Brattain M. G. TGF-beta 1 is an autocrine-negative growth regulator of human colon carcinoma FET cells in vivo as revealed by transfection of an antisense expression vector. J Cell Biol. 1992 Jan;116(1):187–196. doi: 10.1083/jcb.116.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Bacteriology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES