Abstract
A population of bacteria growing in a nonlimiting medium includes mutator bacteria and transient mutators defined as wild-type bacteria which, due to occasional transcription or translation errors, display a mutator phenotype. A semiquantitative theoretical analysis of the steady-state composition of an Escherichia coli population suggests that true strong genotypic mutators produce about 3 X 10(-3) of the single mutations arising in the population, while transient mutators produce at least 10% of the single mutations and more than 95% of the simultaneous double mutations. Numbers of mismatch repair proteins inherited by the offspring, proportions of lethal mutations and mortality rates are among the main parameters that influence the steady-state composition of the population. These results have implications for the experimental manipulation of mutation rates and the evolutionary fixation of frequent but nearly neutral mutations (e.g., synonymous codon substitutions).
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- Biswas D. K., Gorini L. Restriction, de-restriction and mistranslation in missense suppression. Ribosomal discrimination of transfer RNA's. J Mol Biol. 1972 Feb 28;64(1):119–134. doi: 10.1016/0022-2836(72)90324-5. [DOI] [PubMed] [Google Scholar]
- Blank A., Gallant J. A., Burgess R. R., Loeb L. A. An RNA polymerase mutant with reduced accuracy of chain elongation. Biochemistry. 1986 Oct 7;25(20):5920–5928. doi: 10.1021/bi00368a013. [DOI] [PubMed] [Google Scholar]
- Bouadloun F., Donner D., Kurland C. G. Codon-specific missense errors in vivo. EMBO J. 1983;2(8):1351–1356. doi: 10.1002/j.1460-2075.1983.tb01591.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caillet J., Droogmans L. Molecular cloning of the Escherichia coli miaA gene involved in the formation of delta 2-isopentenyl adenosine in tRNA. J Bacteriol. 1988 Sep;170(9):4147–4152. doi: 10.1128/jb.170.9.4147-4152.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cairns J., Overbaugh J., Miller S. The origin of mutants. Nature. 1988 Sep 8;335(6186):142–145. doi: 10.1038/335142a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Damagnez V., Doutriaux M. P., Radman M. Saturation of mismatch repair in the mutD5 mutator strain of Escherichia coli. J Bacteriol. 1989 Aug;171(8):4494–4497. doi: 10.1128/jb.171.8.4494-4497.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drake J. W. A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160–7164. doi: 10.1073/pnas.88.16.7160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fersht A. R., Knill-Jones J. W. Fidelity of replication of bacteriophage phi X174 DNA in vitro and in vivo. J Mol Biol. 1983 Apr 25;165(4):633–654. doi: 10.1016/s0022-2836(83)80271-x. [DOI] [PubMed] [Google Scholar]
- 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]
- Gallant J., Palmer L. Error propagation in viable cells. Mech Ageing Dev. 1979 Apr;10(1-2):27–38. doi: 10.1016/0047-6374(79)90068-x. [DOI] [PubMed] [Google Scholar]
- Glass R. E., Nene V., Hunter M. G. Informational suppression as a tool for the investigation of gene structure and function. Biochem J. 1982 Apr 1;203(1):1–13. doi: 10.1042/bj2030001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hall B. G. Adaptive evolution that requires multiple spontaneous mutations: mutations involving base substitutions. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5882–5886. doi: 10.1073/pnas.88.13.5882. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall B. G. Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics. 1990 Sep;126(1):5–16. doi: 10.1093/genetics/126.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lahue R. S., Au K. G., Modrich P. DNA mismatch correction in a defined system. Science. 1989 Jul 14;245(4914):160–164. doi: 10.1126/science.2665076. [DOI] [PubMed] [Google Scholar]
- Langridge J. Mutation spectra and the neutrality of mutations. Aust J Biol Sci. 1974 Jun;27(3):309–319. doi: 10.1071/bi9740309. [DOI] [PubMed] [Google Scholar]
- Libby R. T., Gallant J. A. The role of RNA polymerase in transcriptional fidelity. Mol Microbiol. 1991 May;5(5):999–1004. doi: 10.1111/j.1365-2958.1991.tb01872.x. [DOI] [PubMed] [Google Scholar]
- Maruyama M., Horiuchi T., Maki H., Sekiguchi M. A dominant (mutD5) and a recessive (dnaQ49) mutator of Escherichia coli. J Mol Biol. 1983 Jul 15;167(4):757–771. doi: 10.1016/s0022-2836(83)80109-0. [DOI] [PubMed] [Google Scholar]
- McHenry C. S. The asymmetric dimeric polymerase hypothesis: a progress report. Biochim Biophys Acta. 1988 Dec 20;951(2-3):240–248. doi: 10.1016/0167-4781(88)90092-9. [DOI] [PubMed] [Google Scholar]
- Ninio J. Kinetic devices in protein synthesis, DNA replication, and mismatch repair. Cold Spring Harb Symp Quant Biol. 1987;52:639–646. doi: 10.1101/sqb.1987.052.01.073. [DOI] [PubMed] [Google Scholar]
- Novick A., Weiner M. ENZYME INDUCTION AS AN ALL-OR-NONE PHENOMENON. Proc Natl Acad Sci U S A. 1957 Jul 15;43(7):553–566. doi: 10.1073/pnas.43.7.553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Farrell P. H. The suppression of defective translation by ppGpp and its role in the stringent response. Cell. 1978 Jul;14(3):545–557. doi: 10.1016/0092-8674(78)90241-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Parker J. Errors and alternatives in reading the universal genetic code. Microbiol Rev. 1989 Sep;53(3):273–298. doi: 10.1128/mr.53.3.273-298.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberger R. F., Hilton J. The frequency of transcriptional and translational errors at nonsense codons in the lacZ gene of Escherichia coli. Mol Gen Genet. 1983;191(2):207–212. doi: 10.1007/BF00334815. [DOI] [PubMed] [Google Scholar]
- Schaaper R. M., Danforth B. N., Glickman B. W. Mechanisms of spontaneous mutagenesis: an analysis of the spectrum of spontaneous mutation in the Escherichia coli lacI gene. J Mol Biol. 1986 May 20;189(2):273–284. doi: 10.1016/0022-2836(86)90509-7. [DOI] [PubMed] [Google Scholar]
- Spudich J. L., Koshland D. E., Jr Non-genetic individuality: chance in the single cell. Nature. 1976 Aug 5;262(5568):467–471. doi: 10.1038/262467a0. [DOI] [PubMed] [Google Scholar]
- Stahl F. W. Bacterial genetics. A unicorn in the garden. Nature. 1988 Sep 8;335(6186):112–113. doi: 10.1038/335112a0. [DOI] [PubMed] [Google Scholar]
- Strigini P., Gorini L. Ribosomal mutations affecting efficiency of amber suppression. J Mol Biol. 1970 Feb 14;47(3):517–530. doi: 10.1016/0022-2836(70)90319-0. [DOI] [PubMed] [Google Scholar]
- Tai P. C., Wallace B. J., Davis B. D. Streptomycin causes misreading of natural messenger by interacting with ribosomes after initiation. Proc Natl Acad Sci U S A. 1978 Jan;75(1):275–279. doi: 10.1073/pnas.75.1.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tröbner W., Piechocki R. Selection against hypermutability in Escherichia coli during long term evolution. Mol Gen Genet. 1984;198(2):177–178. doi: 10.1007/BF00328720. [DOI] [PubMed] [Google Scholar]