ArticleProceedings of the National Academy of Sciences of the United States of America2002
Amplification-mutagenesis: evidence that "directed" adaptive mutation and general hypermutability result from growth with a selected gene amplification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
75 citing papers in PubMed, 174 citations in OpenAlex.
- Article
- Efficient mathematical methodology to determine multistep mutant burden in spatially growing cell populations.PNAS nexus · 2025Article
- How enzyme functions evolve: genetic, structural, and kinetic perspectives.Biophysical reviews · 2025Review
- Review
- Molecular Detection and Genetic Characterization ofAnimals : an open access journal from MDPI · 2022Article
- Article
- Discovery of positive and purifying selection in metagenomic time series of hypermutator microbial populations.PLoS genetics · 2022Article
- Quantum aspects of evolution: a contribution towards evolutionary explorations of genotype networks via quantum walks.Journal of the Royal Society, Interface · 2020Article
- Inactivation of Genes by Frameshift Mutations Provides Rapid Adaptation of an Attenuated Vaccinia Virus.Journal of virology · 2020Article
- Role of Mfd and GreA in Bacillus subtilis Base Excision Repair-Dependent Stationary-Phase Mutagenesis.Journal of bacteriology · 2020Article
- Selective Inbreeding: Genetic Crosses Drive Apparent Adaptive Mutation in the Cairns-Foster System ofGenetics · 2020Article
- Emergence of Concurrent MultipleJCO precision oncology · 2020Article
- Complex DNA structures trigger copy number variation across the Plasmodium falciparum genome.Nucleic acids research · 2019Article
- Selection-Enhanced Mutagenesis ofGenetics · 2018Article
- Affected chromosome homeostasis and genomic instability of clonal yeast cultures.Current genetics · 2016Article
- Article
- Experimental Evolution Identifies Vaccinia Virus Mutations in A24R and A35R That Antagonize the Protein Kinase R Pathway and Accompany Collapse of an Extragenic Gene Amplification.Journal of virology · 2015Article
- The Origin of Mutants Under Selection: How Natural Selection Mimics Mutagenesis (Adaptive Mutation).Cold Spring Harbor perspectives in biology · 2015Review
- Evolution of new functions de novo and from preexisting genes.Cold Spring Harbor perspectives in biology · 2015Review
- Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
When a particular lac mutant of Escherichia coli starves in the presence of lactose, nongrowing cells appear to direct mutations preferentially to sites that allow growth (adaptive mutation). This observation suggested that growth limitation stimulates mutability. Evidence is provided here that this behavior is actually caused by a standard Darwinian process in which natural selection acts in three sequential steps. First, growth limitation favors growth of a subpopulation with an amplification of the mutant lac gene; next, it favors cells with a lac(+) revertant allele within the amplified array. Finally, it favors loss of mutant copies until a stable haploid lac(+) revertant arises and overgrows the colony. By increasing the lac copy number, selection enhances the likelihood of reversion within each developing clone. This sequence of events appears to direct mutations to useful sites. General mutagenesis is a side-effect of growth with an amplification (SOS induction). The F' plasmid, which carries lac, contributes by stimulating gene duplication and amplification. Selective stress has no direct effect on mutation rate or target specificity, but acts to favor a succession of cell types with progressively improved growth on lactose. The sequence of events--amplification, mutation, segregation--may help to explain both the origins of some cancers and the evolution of new genes under selection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.