Key Points
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'Adaptive' mutation denotes a collection of stress responses that include the induction of spontaneous mutation mechanisms in slowly growing or non-growing cells. In adaptive mutation, some of the mutations generated enable these cells to grow.
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It was suggested initially that mutations were directed specifically to genes under selection; however, this idea has not been supported in the few examples studied.
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The adaptive reversion of an episomal lac frameshift allele in Escherichia coli involves both gene (point) mutations that revert the frameshift and amplifications of the weakly functional lac allele.
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The mechanisms of adaptive mutation in the lac system differ from spontaneous mutation in growing cells in that the former involve DNA recombination and repair proteins, the SOS response to DNA damage (cell-cycle checkpoint control), the special error-prone DNA polymerase pol IV (or DinB) and transient limitation of mismatch repair function.
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The F′ conjugative plasmid contributes to adaptive mutation, but recombination-protein-dependent mutation also occurs in the bacterial chromosome.
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In the lac system, some or all adaptive mutants arise from a small subpopulation of cells in which hypermutation at other sites has occurred. There are hot and cold spots for this genome-wide mutation.
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Other bacterial and yeast systems show additional types of stationary- phase and adaptive mutation mechanisms. These include transposon-mediated mutation and transcription-associated mutation.
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Mutation using similar mechanisms might occur in somatic hypermutation of immunoglobulin genes, in mutations associated with double-stranded-break repair in yeast and in phase variation of microbial pathogens.
Abstract
A basic principle of genetics is that the likelihood that a particular mutation occurs is independent of its phenotypic consequences. The concept of adaptive mutation seemed to challenge this principle with the discoveries of mutations stimulated by stress, some of which allow adaptation to the stress. The emerging mechanisms of adaptive genetic change cast evolution, development and heredity into a new perspective, indicating new models for the genetic changes that fuel these processes.
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Acknowledgements
I apologize to my many colleagues whose relevant papers I could not cite owing to space limitations. Thanks to P. J. Hastings, S. Jinks-Robertson, M.-J. Lombardo, N. Maizels and B. Wright for discussions; C. Dorman and J. Strathern for communicating unpublished results; and W. Arber, J. Drake, E. Friedberg, P. J. Hastings, M.-J. Lombardo, G. J. McKenzie, J. Ninio, J. Petrosino and E. Witkin for comments on the manuscript. Supported by grants from the National Institutes of Health (USA).
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FURTHER INFORMATION
Fluctuation test of Luria and Delbrück
ENCYCLOPEDIA OF LIFE SCIENCES
Recombinational DNA repair in bacteria: postreplication
Eukaryotic recombination: initiation by double-strand breaks
Glossary
- AMBER MUTATION
-
A mutation due to the introduction of a stop codon (UAG) in the coding sequence of a gene that results in premature termination of translation.
- POINT MUTATIONS
-
Small changes to DNA, such as base substitutions, small deletion and insertion (frameshift) mutations, made in the context of a gene. They are contrasted here with large-scale genome rearrangements such as gene amplifications and large deletions, inversions, translocations and chromosomal instability.
- F′ CONJUGATIVE PLASMID
-
The F plasmid is a 100-kb extrachromosomal DNA replicon in bacteria that is transmissible between bacteria through conjugation (a specialized sexual process requiring cell–cell contact and mediated by conjugative plasmid-encoded proteins). F′ conjugative plasmids are F conjugative plasmids that have acquired, through recombination, a segment of DNA from the bacterial chromosome.
- PHASE-VARIABLE PATHOGENS
-
Pathogenic microorganisms (both bacterial and eukaryotic) that evade the host immune system by frequent variation of their surface components (proteins, carbohydrates and lipids), called phase variation. The phase variations can be promoted by genetic changes, including mutation and recombination.
- EPISOME
-
A replicon that can exist either extrachromosomally or when integrated into the bacterial chromosome.
- REGRESSED REPLICATION FORK
-
A replication fork that, upon pausing (stalling) of replication, isomerizes such that the newly synthesized daughter strands base-pair with each other (not the templates on which they were synthesized).
- DNA GYRASE
-
An enzyme that relieves supercoiling in DNA by creating a transient break in the double helix.
- TEMPLATE SLIPPAGE
-
A model for the mechanism of frameshift mutation in which a DNA polymerase jumps to an incorrect next place on the template DNA during synthesis, thereby either adding or deleting bases in the nascent strand, the complements of which were present in the template.
- POLAR ALLELE
-
A mutant allele of a gene that decreases or eliminates the expression of additional gene(s) downstream. Polar alleles are common in prokaryotic operons (groups of genes transcribed in a single mRNA).
- NUCLEOID
-
Region in prokaryotes in which the DNA is concentrated. Unlike a nucleus, it is not bound by a membrane.
- CONJUGATIVE TRANSFER
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A specific process by which proteins encoded by the conjugative plasmid DNA (transfer or Tra proteins) allow passage of conjugative plasmid DNA, and any DNA contiguous with it, into another bacterium.
- TOPOISOMERASES
-
Enzymes of two types that can remove (or create) supercoiling in duplex DNA by creating transitory breaks in one (type I) or both (type II) strands of the sugar-phosphate backbone.
- BACTERIOSTATIC
-
Capable of inhibiting bacterial growth (but not necessarily capable of killing bacteria).
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Rosenberg, S. Evolving responsively: adaptive mutation. Nat Rev Genet 2, 504–515 (2001). https://doi.org/10.1038/35080556
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DOI: https://doi.org/10.1038/35080556
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