Jacob Van Oorschot
Project
Clonal interference and the fate of synonymous mutationsSynonymous mutations are often assumed to have no noticeable effect on phenotype. However, mounting evidence suggests synonymous mutations that can affect fitness may arise often. Putative mechanisms to explain these effects include codon bias and gene expression altered at the level of transcription or translation. Nonetheless, beneficial synonymous mutations are recovered less frequently in evolution experiments than expected from site-directed mutagenesis experiments for reasons that remain unclear. Here, we test the hypothesis that the depletion of adaptive synonymous mutations in microbial experimental evolution is the result of high mutation supply rates generating clonal interference, resulting in the enrichment of the more abundant class of large effect nonsynonymous mutations. To test this idea we evolved Pseudomonas fluorescens for 600 generations in low glucose, a condition where beneficial synonymous mutations that create internal promoter sites in a glucose uptake operon had previously been observed, across varying mutation supply rates. Sequencing evolved populations reveals the prevalence of nonsynonymous and synonymous mutations to evaluate the prediction that synonymous mutations will be more prevalent when mutation supply rates, and so clonal interference, are low. Our results emphasize that synonymous mutations are not always neutral and shed light on the conditions under which synonymous mutations contribute to adaptation.
