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

Author:

McGrath Kaitlyn M.123ORCID,Russell Steven J.1ORCID,Fer Evrim14ORCID,Garmendia Eva5ORCID,Hosgel Ali1,Baltrus David A.3ORCID,Kaçar Betül1ORCID

Affiliation:

1. Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA

2. Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, USA

3. School of Plant Sciences, University of Arizona, Tucson, Arizona, USA

4. Microbial Doctoral Training Program, University of Wisconsin-Madison, Madison, Wisconsin, USA

5. Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

Abstract

ABSTRACT 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. IMPORTANCE This study explores the degree to which synonymous mutations in essential genes can influence adaptation in bacteria. An experimental system whereby an Escherichia coli strain harboring an engineered translation protein elongation factor-Tu (EF-Tu) was subjected to laboratory evolution. We find that a synonymous mutation acquired on the gene encoding for EF-Tu is conditionally beneficial for bacterial fitness. Our findings provide insight into the importance of the genetic background when a synonymous substitution is favored by natural selection and how such changes have the potential to impact evolution when critical cellular processes are involved.

Funder

HHS | National Institutes of Health

John Templeton Foundation

NASA | NASA Astrobiology Institute

University of Wisconsin Foundation

Publisher

American Society for Microbiology

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