{"doi":"10.1371/journal.pbio.0020399","title":"Adaptive Amplification and Point Mutation Are Independent Mechanisms: Evidence for Various Stress-Inducible Mutation Mechanisms","abstract":null,"journal":"PLoS Biology","year":2004,"id":606392,"datarank":0.6716005221717312,"base_score":4.477336814478207,"endowment":4.477336814478207,"self_citation_contribution":0.6716005221717312,"citation_network_contribution":0.0,"self_endowment_contribution":0.6716005221717312,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":87,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":661146,"name":"Andrew Slack","orcid":null,"position":1,"is_corresponding":false},{"id":1529540,"name":"Joseph F Petrosino","orcid":null,"position":2,"is_corresponding":false},{"id":1556736,"name":"Susan M Rosenberg","orcid":null,"position":3,"is_corresponding":false},{"id":1556735,"name":"P. J Hastings","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Adaptive Amplification and Point Mutation Are Independent Mechanisms: Evidence for Various Stress-Inducible Mutation Mechanisms","abstract":"\"Adaptive mutation\" denotes a collection of processes in which cells respond to growth-limiting environments by producing compensatory mutants that grow well, apparently violating fundamental principles of evolution. In a well-studied model, starvation of stationary-phase lac(-)Escherichia coli cells on lactose medium induces Lac(+)revertants at higher frequencies than predicted by usual mutation models. These revertants carry either a compensatory frameshift mutation or a greater than 20-fold amplification of the leaky lac allele. A crucial distinction between alternative hypotheses for the mechanisms of adaptive mutation hinges on whether these amplification and frameshift mutation events are distinct, or whether amplification is a molecular intermediate, producing an intermediate cell type, in colonies on a pathway to frameshift mutation. The latter model allows the evolutionarily conservative idea of increased mutations (per cell) without increased mutation rate (by virtue of extra gene copies per cell), whereas the former requires an increase in mutation rate, potentially accelerating evolution. To resolve these models, we probed early events leading to rare adaptive mutations and report several results that show that amplification is not the precursor to frameshift mutation but rather is an independent adaptive outcome. (i) Using new high-resolution selection methods and stringent analysis of all cells in very young (micro)colonies (500-10,000 cells), we find that most mutant colonies contain no detectable lac-amplified cells, in contrast with previous reports. (ii) Analysis of nascent colonies, as young as the two-cell stage, revealed mutant Lac(+)cells with no lac-amplified cells present. (iii) Stringent colony-fate experiments show that microcolonies of lac-amplified cells grow to form visible colonies of lac-amplified, not mutant, cells. (iv) Mutant cells do not overgrow lac-amplified cells in microcolonies fast enough to mask the lac-amplified cells. (v)lac-amplified cells are not SOS-induced, as was proposed to explain elevated mutation in a sequential model. (vi) Amplification, and not frameshift mutation, requires DNA polymerase I, demonstrating that mutation is separable from amplification, and also illuminating the amplification mechanism. We conclude that amplification and mutation are independent outcomes of adaptive genetic change. We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression.","is_dataset_classified":null,"base_score":4.477336814478207,"endowment":4.477336814478207,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15550983","pmcid":"PMC529313","openalex_id":"https://openalex.org/W2072457809","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM64022","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM064022","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM053158","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM53158","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM053158-04","title":"MOLECULAR MECHANISM OF ADAPTIVE MUTATION IN E COLI"},{"funder_name":"National Institutes of Health","grant_id":"1R01GM064022-01","title":"Mechanism of adaptive amplification"}],"total_grants":6,"fwci":4.1035,"citation_percentile":0.94134658,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":3},{"year":2015,"count":6},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0020399&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0020399&type=printable","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pbio.0020399","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15550983","host_type":"repository"},{"url":"https://doaj.org/article/a093424f747d4e58bc1f97e58cf9b866","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/529313","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC529313","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC529313?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pbio.0020399","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pbio.0020399","host_type":""}],"fields_of_study":["Evolution and Genetic Dynamics","RNA and protein synthesis mechanisms","CRISPR and Genetic Engineering","0301 basic medicine","03 medical and health sciences","0303 health sciences","Adaptation, Biological","Alleles","Binding, Competitive","DNA Polymerase I","Escherichia coli","Escherichia coli Proteins","Evolution, Molecular","Frameshift Mutation","Gene Expression Regulation, Bacterial","Genes, Reporter","Green Fluorescent Proteins","Lactose","Molecular Sequence Data","Mutagenesis","Mutation","Phenotype","Point Mutation","SOS Response, Genetics","Selection, Genetic"],"mesh_terms":["Adaptation, Biological","Alleles","Binding, Competitive","DNA Polymerase I","Escherichia coli","Lactose","Molecular Sequence Data","Mutation","Phenotype","Selection, Genetic","SOS Response, Genetics","Gene Expression Regulation, Bacterial","Mutagenesis","Frameshift Mutation","Point Mutation","Genes, Reporter","Evolution, Molecular","Escherichia coli Proteins","Green Fluorescent Proteins"],"keywords":["Biology","Mutation","Point mutation","Genetics","Mechanism (biology)","Adaptive mutation","Gene","Population","QH301-705.5","Green Fluorescent Proteins","Molecular Sequence Data","Adaptation, Biological","Lactose","Binding, Competitive","Evolution, Molecular","Genes, Reporter","Escherichia coli","Biology (General)","Selection, Genetic","Frameshift Mutation","SOS Response, Genetics","Alleles","Escherichia coli Proteins","Gene Expression Regulation, Bacterial","DNA Polymerase I","Phenotype","Mutagenesis","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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