Evidence map›Paper›PMID 24814466›Full record

ArticleGenetics2014

Fitness is strongly influenced by rare mutations of large effect in a microbial mutation accumulation experiment.

Karl Heilbron, Macarena Toll-Riera, Mila Kojadinovic, R Craig MacLean

Open access · bronzeAbstract read
In one paragraph

Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
5.6field-weighted citation impact, top 4% of its field
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

42 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
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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

4 authors at 1 institution in 1 country.

Karl HeilbronDepartment of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom karl.heilbron@zoo.ox.ac.uk.
Macarena Toll-RieraDepartment of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom.
Mila KojadinovicDepartment of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom.
R Craig MacLeanDepartment of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom.
University of Oxford · GB

Funding

Medical Research Council G0900747Medical Research Council G0900747 91070Wellcome TrustWellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments. We performed a classic MA experiment in which frequent sampling of MA lines was combined with whole genome resequencing to develop a high-resolution picture of the effect of spontaneous mutations in a hypermutator (ΔmutS) strain of the bacterium Pseudomonas aeruginosa. After ∼644 generations of mutation accumulation, MA lines had accumulated an average of 118 mutations, and we found that average fitness across all lines decayed linearly over time. Detailed analyses of the dynamics of fitness change in individual lines revealed that a large fraction of the total decay in fitness (42.3%) was attributable to the fixation of rare, highly deleterious mutations (comprising only 0.5% of fixed mutations). Furthermore, we found that at least 0.64% of mutations were beneficial and probably fixed due to positive selection. The majority of mutations that fixed (82.4%) were base substitutions and we failed to find any signatures of selection on nonsynonymous or intergenic mutations. Short indels made up a much smaller fraction of the mutations that were fixed (17.4%), but we found evidence of strong selection against indels that caused frameshift mutations in coding regions. These results help to quantify the amount of natural selection present in microbial MA experiments and demonstrate that changes in fitness are strongly influenced by rare mutations of large effect.

Indexed as

Genetic FitnessBacterial ProteinsDNA, IntergenicGenes, BacterialINDEL MutationMutagenesisMutationOpen Reading FramesPseudomonas aeruginosaSelection, GeneticBacterial ProteinsDNA, Intergenicexperimental evolutionhypermutatorPseudomonas aeruginosaspontaneous mutationwhole genome resequencing

Identifiers

PMID24814466
PMCPMC4096375
OpenAlexW2100874076

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.