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Mol Biol Evol. 2016 Jun;33(6):1542-53. doi: 10.1093/molbev/msw035. Epub 2016 Feb 23.

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

Author information

1
National 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.
2
National Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India.
3
National Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bangalore, India SASTRA University, Thanjavur, India.
4
Department of Microbiology and Molecular Genetics, Michigan State University.
5
Department of Organismic and Evolutionary Biology, Harvard University.
6
Department of Organismic and Evolutionary Biology, Harvard University Systems Biology Graduate Program, Harvard University.
7
Department 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.

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.

KEYWORDS:

Shine–Dalgarno sequence; codon use; epistasis; fitness; mRNA folding.

PMID:
26908584
PMCID:
PMC4868122
DOI:
10.1093/molbev/msw035
[Indexed for MEDLINE]
Free PMC Article

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