Evidence map›Paper›PMID 29133391›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Adaptive benefits from small mutation supplies in an antibiotic resistance enzyme.

Merijn L M Salverda, Jeroen Koomen, Bertha Koopmanschap, Mark P Zwart, J Arjan G M de Visser

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed.

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  12. In vivo hypermutation and continuous evolution.Nature reviews. Methods primers · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Merijn L M SalverdaLaboratory of Genetics, Department of Plant Sciences, Wageningen University, 6708PB Wageningen, The Netherlands.
Jeroen KoomenLaboratory of Genetics, Department of Plant Sciences, Wageningen University, 6708PB Wageningen, The Netherlands.
Bertha KoopmanschapLaboratory of Genetics, Department of Plant Sciences, Wageningen University, 6708PB Wageningen, The Netherlands.
Mark P ZwartLaboratory of Genetics, Department of Plant Sciences, Wageningen University, 6708PB Wageningen, The Netherlands.
J Arjan G M de VisserLaboratory of Genetics, Department of Plant Sciences, Wageningen University, 6708PB Wageningen, The Netherlands; arjan.devisser@wur.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Populations with large mutation supplies adapt via the "greedy" substitution of the fittest genotype available, leading to fast and repeatable short-term responses. At longer time scales, smaller mutation supplies may in theory lead to larger improvements when distant high-fitness genotypes more readily evolve from lower-fitness intermediates. Here we test for long-term adaptive benefits from small mutation supplies using in vitro evolution of an antibiotic-degrading enzyme in the presence of a novel antibiotic. Consistent with predictions, large mutant libraries cause rapid initial adaptation via the substitution of cohorts of mutations, but show later deceleration and convergence. Smaller libraries show on average smaller initial, but also more variable, improvements, with two lines yielding alleles with exceptionally high resistance levels. These two alleles share three mutations with the large-library alleles, which are known from previous work, but also have unique mutations. Replay evolution experiments and analyses of the adaptive landscape of the enzyme suggest that the benefit resulted from a combination of avoiding mutational cohorts leading to local peaks and chance. Our results demonstrate adaptive benefits from limited mutation supplies on a rugged fitness landscape, which has implications for artificial selection protocols in biotechnology and argues for a better understanding of mutation supplies in clinical settings.

Indexed as

MutationAdaptation, PhysiologicalAllelesAnti-Bacterial AgentsBacterial Proteinsbeta-Lactamasesbeta-Lactam ResistanceCefotaximeCloning, MolecularDirected Molecular EvolutionEscherichia coliGene ExpressionGene LibraryGenotypeModels, GeneticPlasmidsAnti-Bacterial AgentsBacterial Proteinsbeta-Lactamasesbeta-lactamase TEM-1CefotaximeRecombinant Proteinsadaptationantibiotic resistanceexperimental evolutionfitness landscapemutation supply

Identifiers

PMID29133391
PMCPMC5715772

What OpenQuestion holds

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Registered trials

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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.