From the site you plagiarised that amazing list from, Tim Harwood's "theory":
"This theory can be described as one of directed mutation."
Shame that Timmy does not keep up with (or apparently read at all) the primary literature - at least he seems to ignore anything to the contrary of his "theory".
If he had, he would know that "directed mutations" aren't.References
Andersson, D. I., E. S. Slechta, et al. (1998). Evidence that gene amplification underlies adaptive mutability of the bacterial lac operon. Science 282(5391): 1133-1135.
Bull, H. J., M. J. Lombardo, et al. (2001). Stationary-phase mutation in the bacterial chromosome: Recombination protein and DNA polymerase IV dependence. Proceedings of the National Academy of Sciences of the United States of America 98(15): 8334-8341.
Bull, H. J., G. J. McKenzie, et al. (2000). Evidence that stationary-phase hypermutation in the Escherichia coli chromosome is promoted by recombination. Genetics 154(4): 1427-1437.
Bull, H. J., G. J. McKenzie, et al. (2000). Response to John Cairns: The contribution of transiently hypermutable cells to mutation in stationary phase. Genetics 156(2): 925-926.
Harris, R. S., H. J. Bull, et al. (1997). A direct role for DNA polymerase III in adaptive reversion of a frameshift mutation in Escherichia coli. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 375(1): 19-24.
Harris, R. S., G. Feng, et al. (1999). Mismatch repair is diminished during stationary-phase mutation. Mutation Research-Reviews in Mutation Research 437(1): 51-60.
Harris, R. S., G. Feng, et al. (1997). Mismatch repair protein MutL becomes limiting during stationary-phase mutation. Genes & Development 11(18): 2426-2437.
Hastings, P. J., H. J. Bull, et al. (2000). Adaptive amplification: An inducible chromosomal instability mechanism. Cell 103(5): 723-731.
Hendrickson, H., E. S. Slechta, et al. (2002). Amplification-mutagenesis: Evidence that "directed" adaptive mutation and general hypermutability result from growth with a selected gene amplification. Proceedings of the National Academy of Sciences of the United States of America 99(4): 2164-2169.
Lombardo, M. J. and S. M. Rosenberg (1999). Hypermutation in stationary-phase E-coli: tales from the lac operon. Journal of Genetics 78(1): 13-20.
Lombardo, M. J., J. Torkelson, et al. (1999). Mechanisms of genome-wide hypermutation in stationary phase. Annals of the New York Academy of Sciences 870: 275-289.
McKenzie, G. J., R. S. Harris, et al. (2000). The SOS response regulates adaptive mutation. Proceedings of the National Academy of Sciences of the United States of America 97(12): 6646-6651.
McKenzie, G. J., P. L. Lee, et al. (2001). SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification. Molecular Cell 7(3): 571-579.
McKenzie, G. J., M. J. Lombardo, et al. (1998). Recombination-dependent mutation in Escherichia coli occurs in stationary phase. Genetics 149(2): 1163-1165.
McKenzie, G. J. and S. M. Rosenberg (2001). Adaptive mutations ; mutator DNA polymerases and genetic change strategies of pathogens. Current Opinion in Microbiology 4(5): 586-594.
Motamedi, M. R., S. K. Szigety, et al. (1999). Double-strand-break repair recombination in Escherichia coli: physical evidence for a DNA replication mechanism in vivo. Genes & Development 13(21): 2889-2903.
Petrosino, J. F., A. R. Pendleton, et al. (2002). Chromosomal system for studying AmpC-mediated beta-lactam resistance mutation in Escherichia coli. Antimicrobial Agents and Chemotherapy 46(5): 1535-1539.
Rosenberg, S. M. (1997). Mutation for survival. Current Opinion in Genetics & Development 7(6): 829-834.
Rosenberg, S. M. (2001). Evolving responsively: Adaptive mutation. Nature Reviews Genetics 2(7): 504-515.
Rosenberg, S. M., C. Thulin, et al. (1998). Transient and heritable mutators in adaptive evolution in the lab and in nature. Genetics 148(4): 1559-1566.
Slechta, E. S., J. Harold, et al. (2002). The effect of genomic position on reversion of a lac frameshift mutation (lacIZ33) during non-lethal selection (adaptive mutation). Molecular Microbiology 44(4): 1017-1032.
Torkelson, J., R. S. Harris, et al. (1997). Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation. Embo Journal 16(11): 3303-3311.
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Quotes from a few:
: EMBO J 1997 Jun 2;16(11):3303-11
: Genome-wide hypermutation in a subpopulation of stationary-phase cells underlies recombination-dependent adaptive mutation.
: Torkelson J, Harris RS, Lombardo MJ, Nagendran J, Thulin C, Rosenberg SM
: Stationary-phase mutation in microbes can produce selected ('adaptive') mutants preferentially. In one system, this occurs via a distinct, recombination-dependent mechanism. Two points of controversy have surrounded these adaptive reversions of an Escherichia coli lac mutation. First, are the mutations directed preferentially to the selected gene in a Lamarckian manner?
: Second, is the adaptive mutation mechanism specific to the F plasmid replicon carrying lac? We report that lac adaptive mutations are associated with hypermutation in unselected genes, in all replicons in the cell. The associated mutations have a similar sequence spectrum to the adaptive reversions. Thus, the adaptive mutagenesis mechanism is not directed to the lac genes, in a Lamarckian manner,nor to the F' replicon carrying lac. Hypermutation was not found in non-revertants exposed to selection. Therefore, the genome-wide hypermutation underlying adaptive mutation occurs in a differentiated subpopulation. The existence of mutable subpopulations in non-growing cells is important in bacterial evolution and could be relevant to the somatic mutations that give rise to cancers in multicellular organisms.
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: "Researchers first noticed this happening in 1988 when John Cairns, then at Harvard University, showed that mutation rates in the bacterium Escherichia coli increased when the microbes needed to evolve new capabilities in order to survive changes in their environment.
: At the time, it seemed that only those genes directly involved with the adaptation changed,and this idea of adapative or directed evolution caused quite a stir.
: But then last year, molecular geneticist Susan Rosenberg at Baylor College of Medicine in Houston and her colleagues showed that mutation rates increase throughout the genome, although only in a subset of the population. Another group also found that more than just the relevant genes changed." (How the Genome Readies Itself for Evolution, Elizabeth Pennisi, Science, vol 281,
: Number 5380, Issue of 21 Aug 1998, p1131-1134)
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: Mutat Res 1999 Jul;437(1):51-60
: Mismatch repair is diminished during stationary-phase mutation.
: Harris RS, Feng G, Ross KJ, Sidhu R, Thulin C, Longerich S, Szigety SK, Hastings PJ, Winkler ME,Rosenberg SM.
: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
: This paper is an invited Response to a recent Commentary [P.L. Foster, Rev. Mut. Res. 436 (1999) 179-184] entitled "Are adaptive mutations due to a decline in mismatch repair? The evidence is lacking". The Commentary argues that no evidence exists supporting the idea that mismatch repair is limiting specifically during stationary-phase mutation. A primary concern of the author is to question the method that we used previously to measure growth-dependent mutation. In this method, mutation rates are calculated using counts of mutant colonies taken at times when those colonies arise, rather than at a predetermined, fixed time. Here we show further data that illustrate why this must be done to ensure accurate mutation measurements. Such accuracy was necessary for our published determination that mismatch repair proteins are not limiting during growth-dependent mutation, but become so during stationary-phase mutation. We review the evidence supporting the idea that stationary-phase reversion of a lac frameshift mutation occurs in an environment of decreased mismatch repair capacity. Those data are substantial. The data presented in the Commentary, in apparent contradiction to this idea, do not justify the conclusion presented there. Copyright 1999 Elsevier Science B.V.
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: Ann N Y Acad Sci 1999 May 18;870:275-89
: Mechanisms of genome-wide hypermutation in stationary phase.
: Lombardo MJ, Torkelson J, Bull HJ, McKenzie GJ, Rosenberg SM.
: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
: Stationary-phase mutation (a subset of which was previously called adaptive mutation) occurs in apparently nondividing, stationary-phase cells exposed to a nonlethal genetic selection. In one experimental system, stationary-phase reversion of an Escherichia coli F'-borne lac frameshift mutation occurs by a novel molecular mechanism that requires homologous recombination functions of the RecBCD system. Chromosomal mutations at multiple loci are detected more frequently in Lac+ stationary-phase revertants than in cells that were also exposed to selection but did not become Lac+. Thus, mutating cells represent a subpopulation that experiences hypermutation throughout the genome. This paper summarizes current knowledge regarding stationary-phase mutation in the lac system. Hypotheses for the mechanism of chromosomal hypermutation are discussed, and data are presented that exclude one hypothetical mechanism in which chromosomal mutations result from Hfr formation.
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: Science 1998 Nov 6;282(5391):1133-5
: Evidence that gene amplification underlies adaptive mutability of the bacterial lac operon.
: Andersson DI, Slechta ES, Roth JR.
: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
: Adaptive mutability is the apparent alteration in specificity or rate of mutability seen in bacteria during stress. A model is proposed by which gene amplification during selective growth can give the appearance of adaptive mutability without requiring any change in mutability. The model is based on two assumptions, that a mutant lac locus with residual function allows growth if its copy number is increased, and that true reversion events are made more likely by replication of chromosomes with many copies of the locus. Apparent directed mutability, its recombination requirement, and its apparent independence of cell growth are all accounted for by the model. Evidence is provided for the required residual function and gene amplification.
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: Mutat Res 2001 Jan 25;473(1):109-19
: Effect of endogenous carotenoids on "adaptive" mutation in Escherichia coli FC40.
: Bridges BA, Foster PL, Timms AR.
: MRC Cell Mutation Unit, University of Sussex, Falmer, BN1 9RR, Brighton, UK. b.a.bridges@sussex.ac.uk
: The appearance over many days of Lac(+) frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent "adaptive" mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases.
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Still have confidence in Harwood's assessments?
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