Evidence map›Paper›PMID 26908584›Full record

ArticleMolecular biology and evolution2016

Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium.

Deepa Agashe, Mrudula Sane, Kruttika Phalnikar, Gaurav D Diwan, Alefiyah Habibullah, Norma Cecilia Martinez-Gomez, Vinaya Sahasrabuddhe, William Polachek, Jue Wang, Lon M Chubiz and 1 more

Abstract read
In one paragraph

Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing 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

40 citing papers in PubMed.

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  10. Conversion ofMicroorganisms · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Deepa AgasheNational Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India Department of Organismic and Evolutionary Biology, Harvard University dagashe@ncbs.res.in cmarx@uidaho.edu.
Mrudula SaneNational Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India.
Kruttika PhalnikarNational Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India.
Gaurav D DiwanNational Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India SASTRA University, Thanjavur, India.
Alefiyah HabibullahNational Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India.
Norma Cecilia Martinez-GomezDepartment of Microbiology and Molecular Genetics, Michigan State University.
Vinaya SahasrabuddheNational Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India.
William PolachekDepartment of Organismic and Evolutionary Biology, Harvard University.
Jue WangDepartment of Organismic and Evolutionary Biology, Harvard University Systems Biology Graduate Program, Harvard University.
Lon M ChubizDepartment of Organismic and Evolutionary Biology, Harvard University.
Christopher J MarxDepartment of Organismic and Evolutionary Biology, Harvard University Faculty of Arts and Sciences Center for Systems Biology, Harvard University Department of Biological Sciences, University of Idaho Institute for Bioinformatics and Evolutionary Studies, University of Idaho dagashe@ncbs.res.in cmarx@uidaho.edu.

Funding

Systems-level physiological basis of selection and epistasis in adaptationR01GM078209 · NIGMS · HARVARD UNIVERSITY · PI MARX, CHRISTOPHER J · 2007 to 2011
$1.7M
NIGMS NIH HHS R01 GM078209
6 · The paper itself

Abstract

Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context.

Indexed as

Genetic FitnessMutationAdaptation, PhysiologicalBacterial ProteinsBiological EvolutionCarbon-Nitrogen LigasesCodonEpistasis, GeneticEvolution, MolecularMethylobacterium extorquensProtein BiosynthesisRibosomesRNA, MessengerSelection, GeneticSilent MutationBacterial ProteinsCarbon-Nitrogen LigasesCodonFae protein, Methylobacterium extorquensRNA, Messengercodon useepistasisfitnessmRNA folding.Shine–Dalgarno sequence

Identifiers

PMID26908584
PMCPMC4868122

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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.