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.
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.
Pseudomonas fluorescens SBW25 gtsB mutantsNCBI Sequence Read Archive, BioProject PRJNA515918.
- Rees Kassen
- Eleonore Lebeuf-Taylor
- Nick McCloskey
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Christian R Landry, Université Laval, Canada
© 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.