Gene Erosion Can Lead to Gain-of-Function Alleles That Contribute to Bacterial Fitness

mBio. 2021 Aug 31;12(4):e0112921. doi: 10.1128/mBio.01129-21. Epub 2021 Jul 6.


Despite our extensive knowledge of the genetic regulation of heat shock proteins (HSPs), the evolutionary routes that allow bacteria to adaptively tune their HSP levels and corresponding proteostatic robustness have been explored less. In this report, directed evolution experiments using the Escherichia coli model system unexpectedly revealed that seemingly random single mutations in its tnaA gene can confer significant heat resistance. Closer examination, however, indicated that these mutations create folding-deficient and aggregation-prone TnaA variants that in turn can endogenously and preemptively trigger HSP expression to cause heat resistance. These findings, importantly, demonstrate that even erosive mutations with disruptive effects on protein structure and functionality can still yield true gain-of-function alleles with a selective advantage in adaptive evolution.

Keywords: evolution; genetics; heat resistance; protein aggregates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Directed Molecular Evolution / methods
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Gain of Function Mutation*
  • Gene Expression Regulation, Bacterial
  • Genetic Fitness*
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Response / genetics
  • Mutation


  • Heat-Shock Proteins