Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates.

Ninio, Jacques

doi:10.1093/genetics/129.3.957

Cited by 143 publications

(48 citation statements)

References 45 publications

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“…Exposure to sublethal doses of streptomycin has long been known to result in inaccurate translation (Balashov et al, 2003;Rosset et al, 1969). As first proposed by Ninio (1991), mistranslation of DNA repair and replication proteins can create transient mutator states. For example, mutations that result in certain mutant tRNAs have mutator phenotypes because the proofreading subunit of the DNA polymerase III holoenzyme is mistranslated, making replication error-prone (Al Mamun et al, 2002;Slupska et al, 1998).…”

Section: Exposure To Antibioticsmentioning

confidence: 99%

Stress-Induced Mutagenesis in Bacteria

Foster

2007

Critical Reviews in Biochemistry and Molecular Biology

460

306

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Bacteria spend their lives buffeted by changing environmental conditions. To adapt to and survive these stresses, bacteria have global response systems that result in sweeping changes in gene expression and cellular metabolism. These responses are controlled by master regulators, which include: alternative sigma factors, such as RpoS and RpoH; small molecule effectors, such as ppGpp; gene repressors such as LexA; and, inorganic molecules, such as polyphosphate. The response pathways extensively overlap and are induced to various extents by the same environmental stresses. These stresses include nutritional deprivation, DNA damage, temperature shift, and exposure to antibiotics. All of these global stress responses include functions that can increase genetic variability. In particular, up-regulation and activation of error-prone DNA polymerases, down-regulation of error-correcting enzymes, and movement of mobile genetic elements are common features of several stress responses. The result is that under a variety of stressful conditions, bacteria are induced for genetic change. This transient mutator state may be important for adaptive evolution.

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Section: Exposure To Antibioticsmentioning

confidence: 99%

Stress-Induced Mutagenesis in Bacteria

Foster

2007

Critical Reviews in Biochemistry and Molecular Biology

460

306

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“…An alternative mechanism that can yield elevated mutation rates with no heritable long-term disadvantage is transient hypermutability, whereby a subset of germline replication events experience elevated levels of mutagenicity associated with an aberrant DNA polymerase/damage repair apparatus or reaction (Ninio 1991;Drake 2007). Stochastic variation associated with transcription or translation errors, erroneous protein folding, nucleotide pool imbalance, and/or metabolic limitations will inevitably generate intercellular variation in mutation rates, but unlike the situation with mutator alleles, the mutagenic conditions will not be heritable.…”

Section: Transient Hypermutabilitymentioning

confidence: 99%

The Rate of Establishment of Complex Adaptations

Lynch

Abegg

2010

Molecular Biology and Evolution

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A central problem in evolutionary theory concerns the mechanisms by which adaptations requiring multiple mutations emerge in natural populations. We develop a series of expressions that clarify the scaling of the time to establishment of complex adaptations with population size, mutation rate, magnitude of the selective disadvantage of intermediate-state alleles, and the complexity of the adaptation. In general, even in the face of deleterious intermediate steps, the time to establishment is minimized in populations with very large size. Under a broad range of conditions, the time to establishment also scales by no more than the square of the mutation rate, regardless of the number of sites contributing to the adaptive change, demonstrating that the emergence of complex adaptations is only weakly constrained by the independent acquisition of mutations at the underlying sites. Mutator alleles with deleterious side effects have only moderate effects on the rate of adaptation in large populations but can cause a quantum decrease in the time to establishment of some adaptive alleles in small populations, although probably not at a high enough rate to offset the increased deleterious mutation load. Transient hypermutability, whereby a subset of gamete-producing cells mutate at an elevated rate in a nonheritable manner, may also elevate the rate of adaptation, although the effect is modest and appears to result from a simple increase in the rate of transitions between intermediate states rather than from the saltational production of doublet mutations. Taken together, these results illustrate the plausibility of the relatively rapid emergence of specific complex adaptations by conventional population genetic mechanisms and provide insight into the relative incidences of various paths of allelic adaptation in organisms with different population genetic features.

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“…Ninio (85) and subsequently Boe (10) have postulated that transcriptional and translational errors could result in error-prone DNA polymerases and defects in DNA error-correcting functions. These would then act as transient mutators.…”

Section: The Hypermutable State-hallmentioning

confidence: 99%

ADAPTIVE MUTATION: The Uses of Adversity

Foster¹

1993

Annu. Rev. Microbiol.

237

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When populations of microorganisms are subjected to certain nonlethal selections, useful mutants arise among the nongrowing cells whereas useless mutants do not. This phenomenon, known as adaptive, directed, or selection-induced mutation, challenges the long-held belief that mutations only arise at random and without regard for utility. In recent years a growing number of studies have examined adaptive mutation in both bacteria and yeast. Although conflicts and controversies remain, the weight of the evidence indicates that adaptive mutation cannot be explained by trivial artifacts and that nondividing cells accumulate mutations in the absence of genomic replication. Because this process tends to produce only useful mutations, the cells appear to have a mechanism for preventing useless genetic changes from occurring or for eliminating them after they occur. The model that most readily explains the evidence is that cells under stress produce genetic variants continuously and at random, but these variants are immortalized as mutations only if they allow the cell to grow.

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Transient mutators: a semiquantitative analysis of the influence of translation and transcription errors on mutation rates.

Cited by 143 publications

References 45 publications

Stress-Induced Mutagenesis in Bacteria

Stress-Induced Mutagenesis in Bacteria

The Rate of Establishment of Complex Adaptations

ADAPTIVE MUTATION: The Uses of Adversity

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