ArticleGenetics2010
Evolution at a high imposed mutation rate: adaptation obscures the load in phage T7.
Article in Genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Fluoroquinolone-specific resistance trajectories in E. coli and their dependence on the SOS-response.BMC microbiology · 2025Article
- Lethal mutagenesis and the transient within-host dynamics of viral adaptation.Virus evolution · 2025Article
- Heat adaptation of phage T7 under an extended genetic code.Virus evolution · 2021Article
- λ Recombineering Used to Engineer the Genome of Phage T7.Antibiotics (Basel, Switzerland) · 2020Article
- Combined Solution and Crystal Methods Reveal the Electrostatic Tethers That Provide a Flexible Platform for Replication Activities in the Bacteriophage T7 Replisome.Biochemistry · 2019Article
- Article
- Dynamics and Fate of Beneficial Mutations Under Lineage Contamination by Linked Deleterious Mutations.Genetics · 2017Article
- Two sides of the same coin: A population genetics perspective on lethal mutagenesis and mutational meltdown.Virus evolution · 2017Article
- Quantitative Modeling of Microbial Population Responses to Chronic Irradiation Combined with Other Stressors.PloS one · 2016Article
- Lethal mutagenesis failure may augment viral adaptation.Molecular biology and evolution · 2014Article
- Genome dynamics during experimental evolution.Nature reviews. Genetics · 2013Review
- Article
- Correlation between mutation rate and genome size in riboviruses: mutation rate of bacteriophage Qβ.Genetics · 2013Article
- Evolution at increased error rate leads to the coexistence of multiple adaptive pathways in an RNA virus.BMC evolutionary biology · 2013Article
- Nucleoside analogue mutagenesis of a single-stranded DNA virus: evolution and resistance.Journal of virology · 2012Article
- Interactions between evolutionary processes at high mutation rates.Evolution; international journal of organic evolution · 2012Article
- Viral quasispecies evolution.Microbiology and molecular biology reviews : MMBR · 2012Review
- Mutational robustness of an RNA virus influences sensitivity to lethal mutagenesis.Journal of virology · 2012Article
- Multiple genetic pathways to similar fitness limits during viral adaptation to a new host.Evolution; international journal of organic evolution · 2012Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Evolution at high mutation rates is expected to reduce population fitness deterministically by the accumulation of deleterious mutations. A high enough rate should even cause extinction (lethal mutagenesis), a principle motivating the clinical use of mutagenic drugs to treat viral infections. The impact of a high mutation rate on long-term viral fitness was tested here. A large population of the DNA bacteriophage T7 was grown with a mutagen, producing a genomic rate of 4 nonlethal mutations per generation, two to three orders of magnitude above the baseline rate. Fitness-viral growth rate in the mutagenic environment-was predicted to decline substantially; after 200 generations, fitness had increased, rejecting the model. A high mutation load was nonetheless evident from (i) many low- to moderate-frequency mutations in the population (averaging 245 per genome) and (ii) an 80% drop in average burst size. Twenty-eight mutations reached high frequency and were thus presumably adaptive, clustered mostly in DNA metabolism genes, chiefly DNA polymerase. Yet blocking DNA polymerase evolution failed to yield a fitness decrease after 100 generations. Although mutagenic drugs have caused viral extinction in vitro under some conditions, this study is the first to match theory and fitness evolution at a high mutation rate. Failure of the theory challenges the quantitative basis of lethal mutagenesis and highlights the potential for adaptive evolution at high mutation rates.
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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.