Adaptive Mutation by Deletions in Small Mononucleotide Repeats

Rosenberg, Susan M.; Longerich, Simonne; Gee, Pauline; Harris, Reuben S.

doi:10.1126/science.8023163

Cited by 218 publications

(219 citation statements)

References 30 publications

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“…That it was not implies that the recG defect affects the frequency of a mutagenic process, but not the probability of any given mutation occurring during this process. For example, both Lac ϩ and Tet r mutations may be produced during DNA synthesis initiated or preserved by recombination (15,41); the recombination functions may alter the frequency of such events, but the probability of one or both mutations being produced would depend only on the accuracy of the DNA synthesis. A less specific hypothesis is that both Lac ϩ and Tet r mutations occur within a subpopulation of highly mutating cells, and the recombination functions determine the number of these cells but not their mutation rate.…”

Section: Discussionmentioning

confidence: 99%

Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli

1997

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One of the most studied examples of adaptive mutation is a strain of Escherichia coli, FC40, that cannot utilize lactose (Lac ؊ ) but that readily reverts to lactose utilization (Lac ؉ ) when lactose is its sole carbon source. Adaptive reversion to Lac ؉ occurs at a high rate when the Lac ؊ allele is on an F episome and conjugal functions are expressed. It was previously shown that nonselected mutations on the chromosome did not appear in the Lac ؊ population while episomal Lac ؉ mutations accumulated, but it remained possible that nonselected mutations might occur on the episome. To investigate this possibility, a second mutational target was created on the Lac ؊ episome by mutation of a Tn10 element, which encodes tetracycline resistance (Tet r ), to tetracycline sensitivity (Tet s ). Reversion rates to Tet r during normal growth and during lactose selection were measured. The results show that nonselected Tet r mutations do accumulate in Lac ؊ cells when those cells are under selection to become Lac ؉ . Thus, reversion to Lac ؉ in FC40 does not appear to be adaptive in the narrow sense of the word. In addition, the results suggest that during lactose selection, both Lac ؉ and Tet r mutations are created or preserved by the same recombination-dependent mechanism.Mutations occurring in nondividing cells have been called adaptive when they allow cells to escape from nonlethal selective pressure (5,7,20). A narrower definition of adaptive mutation is that only useful, not deleterious or neutral, mutations occur during selection (7,12,29). A number of possible examples of such specifically adaptive mutations have been reported (7,13,21,22,24,44). Most current theories for adaptive mutation propose that cells under selection produce genetic variants at random, but these variants are transient, or the cells producing them die, unless a useful mutation occurs and the cells start to grow (3,7,22,43). All of these models predict that nonselected mutations may appear in the successful cells (because all variants that exist when a cell begins to grow will be captured), but nonselected mutations should not appear in the unsuccessful cells (reviewed in reference 12).One of the most studied examples of adaptive mutation is a strain of Escherichia coli, FC40, that cannot utilize lactose (Lac Ϫ ) but that readily reverts to lactose utilization (Lac ϩ ) when lactose is its sole carbon source (5). This high level of adaptive reversion occurs when the Lac Ϫ allele is on an FЈ episome and conjugal functions are expressed (17,19,39). Although mutations in a chromosomal gene, rpoB, do not appear in the Lac Ϫ population while episomal Lac ϩ mutations accumulate (13), the question remained whether nonselected mutations might occur on the episome. Here, I report that, indeed, nonselected mutations at another site on FЈ accumulate in Lac Ϫ cells when those cells are under selection to become Lac ϩ . Thus, any given gene on the episome may be subjected to a highly mutagenic process in cells under nonlethal selective pressure. Although t...

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Section: Discussionmentioning

confidence: 99%

Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli

1997

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“…The DNA sequence changes that give rise to adaptive Lac + mutations and growthdependent Lac + mutations are different. Adaptive Lac + mutations are almost all −1 bp frameshifts in runs of iterated bases [47,48], whereas growth-dependent mutations include deletions, duplications, and other frameshifts.…”

Section: The Genetics Of Adaptive Mutationmentioning

confidence: 99%

Stress responses and genetic variation in bacteria

Foster

2005

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

178

106

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Under stressful conditions mechanisms that increase genetic variation can bestow a selective advantage. Bacteria have several stress responses that provide ways in which mutation rates can be increased. These include the SOS response, the general stress response, the heat-shock response, and the stringent response, all of which impact the regulation of error-prone polymerases. Adaptive mutation appears to be process by which cells can respond to selective pressure specifically by producing mutations. In Escherichia coli strain FC40 adaptive mutation involves the following inducible components: (i) a recombination pathway that generates mutations; (ii) a DNA polymerase that synthesizes error-containing DNA; and (iii) stress responses that regulate cellular processes. In addition, a subpopulation of cells enters into a state of hypermutation, giving rise to about 10% of the single mutants and virtually all of the mutants with multiple mutations. These bacterial responses have implications for the development of cancer and other genetic disorders in higher organisms.

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“…While a variety of deletions, duplications, and frameshifts revert the Lac Ϫ allele during growth, adaptive Lac ϩ mutations consist almost exclusively of Ϫ1-bp frameshifts in runs of iterated bases (27,61).…”

Section: Genetics Of Adaptive Mutationmentioning

confidence: 99%

Adaptive Mutation in Escherichia coli

Foster¹

2000

Cold Spring Harbor Symposia on Quantitative Biology

102

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In 1988 John Cairns, Julie Overbaugh, and Stephan Miller published a paper entitled "The origin of mutants," in which they suggested that bacteria could choose which mutations to make (11). Shortly thereafter, Cairns and I began collaborating on a National Science Foundation-funded project to investigate the genetic basis of what was popularly called "directed mutation" (although at the time we were calling it "selectiondependent mutation," which now seems as good a name as any). Our plan was to mutagenize an appropriate strain of Escherichia coli and identify and characterize variants defective in selection-dependent mutation. Cairns and coworkers had been investigating a strain called SM195, described in their original paper (11). However, the mechanisms of mutation in this strain had proved to be complicated, and we wanted a new experimental subject. We were setting up to investigate selection-induced activation of the cryptic bgl operon (36), when Jeffrey Miller gave us a Lac Ϫ strain, called ␣45, that he said had a high rate of reversion to Lac ϩ after plating on minimum lactose medium. The lac allele in this strain is a fusion of lacI to lacZ that eliminates the lac regulatory region as well as several residues of lacI and lacZ; transcription of the fusion is constitutive, initiating at the lacI promoter (7). ␣45 has a ϩ1 frameshift mutation, lacI33, in the lacI coding region (12). Miller and coworkers have used several similar strains to study various mutational mechanisms (52, 67). As in many of the strains that originated with Jacob and Monod, proAB and lac are deleted from the chromosome and carried on an episome, FЈ128. This arrangement greatly facilitates genetic manipulations and turned out to be important to adaptive mutation. We mated the episome from ␣45 into a ⌬(lac-pro) recipient that we had made rifampin resistant and named the new strain FC40 (Foster and Cairns #40).In our first paper (10), we showed that Lac ϩ revertants of FC40 accumulate at a constant rate for about a week after the cells are plated on minimal lactose plates. Two days after plating (the first day that Lac ϩ colonies appear), the numbers of mutants among cultures has a Luria-Delbrück distribution (meaning that the mutations occurred prior to plating), whereas on subsequent days the distribution becomes Poisson (meaning that the mutations occurred after plating). After 5 days on lactose plates, there are about 100 Lac ϩ colonies per 10 8 cells plated. We calculated that the normal preplating mutation rate was about 10 Ϫ9 Lac ϩ revertants per cell per generation, whereas the postplating mutation rate was about 10 Ϫ9 per cell per h; considering that the doubling time in minimal medium is about an hour, this means that per unit time, the two mutation rates are the same. We have never figured out if this similarity is informative or merely a coincidence.The high postplating reversion rate of FC40 allowed us to eliminate a number of artifactual explanations for the phenomenon. In our first paper (10) we ruled out the possibility ...

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Adaptive Mutation by Deletions in Small Mononucleotide Repeats

Cited by 218 publications

References 30 publications

Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli

Nonadaptive mutations occur on the F' episome during adaptive mutation conditions in Escherichia coli

Stress responses and genetic variation in bacteria

Adaptive Mutation in Escherichia coli

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