Abstract
Recent reports have called into question the widespread belief ``that mutations arise continuously and without any consideration for their utility'' (in the words of J. Cairns) and have suggested that some mutations (which Cairns called ``directed'' mutations) may occur as specific responses to environmental challenges, i.e., they may occur more often when advantageous than when neutral. In this paper it is shown that point mutations in the trp operon reverted to trp(+) more frequently under conditions of prolonged tryptophan deprivation when the reversions were advantageous, than in the presence of tryptophan when the reversions were neutral. The overall mutation rate, as determined from the rates of mutation to valine resistance and to constitutive expression of the lac operon, did not increase during tryptophan starvation. The trp reversion rate did not increase when the cells were starved for cysteine for a similar period, indicating that the increased reversion rate was specific to conditions where the reversions were advantageous. Two artifactual explanations for the observations, delayed growth of some preexisting revertants and cryptic growth by some cells at the expense of dying cells within aged colonies, were tested and rejected as unlikely. The trp(+) reversions that occurred while trp(-) colonies aged in the absence of tryptophan were shown to be time-dependent rather than replication-dependent, and it is suggested that they occur by mechanisms different from those that have been studied in growing cells. A heuristic model for the molecular basis of such mutations is proposed and evidence consistent with that model is discussed. It is suggested that the results in this and previous studies can be explained on the basis of underlying random mechanisms that act during prolonged periods of physiological stress, and that ``directed'' mutations are not necessarily the basis of those observations.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Davis B. D. Transcriptional bias: a non-Lamarckian mechanism for substrate-induced mutations. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5005–5009. doi: 10.1073/pnas.86.13.5005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drake J. W. Comparative rates of spontaneous mutation. Nature. 1969 Mar 22;221(5186):1132–1132. doi: 10.1038/2211132a0. [DOI] [PubMed] [Google Scholar]
- Hall B. G. Adaptive evolution that requires multiple spontaneous mutations. I. Mutations involving an insertion sequence. Genetics. 1988 Dec;120(4):887–897. doi: 10.1093/genetics/120.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall B. G., Betts P. W., Wootton J. C. DNA sequence analysis of artificially evolved ebg enzyme and ebg repressor genes. Genetics. 1989 Dec;123(4):635–648. doi: 10.1093/genetics/123.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall B. G., Clarke N. D. Regulation of newly evolved enzymes. III Evolution of the ebg repressor during selection for enhanced lactase activity. Genetics. 1977 Feb;85(2):193–201. doi: 10.1093/genetics/85.2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hall B. G. Selection, adaptation, and bacterial operons. Genome. 1989;31(1):265–271. doi: 10.1139/g89-044. [DOI] [PubMed] [Google Scholar]
- Kricker M., Hall B. G. Directed evolution of cellobiose utilization in Escherichia coli K12. Mol Biol Evol. 1984 Feb;1(2):171–182. doi: 10.1093/oxfordjournals.molbev.a040310. [DOI] [PubMed] [Google Scholar]
- Lenski R. E., Slatkin M., Ayala F. J. Mutation and selection in bacterial populations: alternatives to the hypothesis of directed mutation. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2775–2778. doi: 10.1073/pnas.86.8.2775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mellon I., Hanawalt P. C. Induction of the Escherichia coli lactose operon selectively increases repair of its transcribed DNA strand. Nature. 1989 Nov 2;342(6245):95–98. doi: 10.1038/342095a0. [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]
- Schaaper R. M., Dunn R. L. Spectra of spontaneous mutations in Escherichia coli strains defective in mismatch correction: the nature of in vivo DNA replication errors. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6220–6224. doi: 10.1073/pnas.84.17.6220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shapiro J. A. Observations on the formation of clones containing araB-lacZ cistron fusions. Mol Gen Genet. 1984;194(1-2):79–90. doi: 10.1007/BF00383501. [DOI] [PubMed] [Google Scholar]
- Slater J. H., Weightman A. J., Hall B. G. Dehalogenase genes of Pseudomonas putida PP3 on chromosomally located transposable elements. Mol Biol Evol. 1985 Nov;2(6):557–567. doi: 10.1093/oxfordjournals.molbev.a040366. [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]
- Symonds N. Evolution. Anticipatory mutagenesis. Nature. 1989 Jan 12;337(6203):119–120. doi: 10.1038/337119a0. [DOI] [PubMed] [Google Scholar]