The distribution of fitness effects among synonymous mutations in a gene under directional selection
Abstract
The fitness effects of synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have often been assumed to be neutral, but a growing body of evidence suggests otherwise. We used site-directed mutagenesis coupled with direct measures of competitive fitness to estimate the distribution of fitness effects among synonymous mutations for a gene under directional selection and capable of adapting via synonymous nucleotide changes. Synonymous mutations had highly variable fitness effects, both deleterious and beneficial, resembling those of nonsynonymous mutations in the same gene. This variation in fitness was underlain by changes in transcription linked to the creation of internal promoter sites. A positive correlation between fitness and the presence of synonymous substitutions across a phylogeny of related Pseudomonads suggests these mutations may be common in nature. Taken together, our results provide the most compelling evidence to date that synonymous mutations with non-neutral fitness effects may in fact be commonplace.
Data availability
Genomic data has been deposited into the NCBI Sequence Read Archive as BioProject PRJNA515918. All other data generated during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, and 3.
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Pseudomonas fluorescens SBW25 gtsB mutantsNCBI Sequence Read Archive, BioProject PRJNA515918.
Article and author information
Author details
Funding
Natural Sciences and Engineering Research Council of Canada (Discovery Grant)
- Rees Kassen
Natural Sciences and Engineering Research Council of Canada (Canada Graduate Scholarship)
- Eleonore Lebeuf-Taylor
Ontario Ministry of Economic Development and Innovation (Ontario Graduate Scholarship)
- Nick McCloskey
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Lebeuf-Taylor et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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