Fitness benefits of a synonymous substitution in an ancient EF-Tu gene depend on the genetic background

Kaitlyn M. McGrath, Steven J. Russell, Evrim Fer, Eva Garmendia, Ali Hosgel, David A. Baltrus, Betül Kaçar

Research output: Contribution to journalArticlepeer-review


Synonymous mutations are changes to DNA sequence, which occur within translated genes but which do not affect the protein sequence. Although often referred to as silent mutations, evidence suggests that synonymous mutations can affect gene expression, mRNA stability, and even translation efficiency. A collection of both experimental and bioinformatic data has shown that synonymous mutations can impact cell phenotype, yet less is known about the molecular mechanisms and potential of beneficial or adaptive effects of such changes within evolved populations. Here, we report a beneficial synonymous mutation acquired via experimental evolution in an essential gene variant encoding the translation elongation factor protein EF-Tu. We demonstrate that this particular synonymous mutation increases EF-Tu mRNA and protein levels as well as global polysome abundance on RNA transcripts. Although presence of the synonymous mutation is clearly causative of such changes, we also demonstrate that fitness benefits are highly contingent on other potentiating mutations present within the genetic background in which the mutation arose. Our results underscore the importance of beneficial synonymous mutations, especially those that affect levels of proteins that are key for cellular processes.

Original languageEnglish (US)
JournalJournal of bacteriology
Issue number2
StatePublished - Feb 2024


  • elongation factor EF-Tu
  • experimental evolution
  • synonymous mutation
  • translation

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology


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