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

Julien Mortier, Elisa Gayán, Ronald Van Eyken, Oscar Enrique Torres Montaguth, Ladan Khodaparast, Laleh Khodaparast, Bert Houben, Sebastien Carpentier, Frederic Rousseau, Joost Schymkowitz, Abram Aertsen

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)


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.

Original languageEnglish
Article numbere01129-21
Pages (from-to)e0112921
Issue number4
Early online date6 Jul 2021
Publication statusPublished - 31 Aug 2021

Bibliographical note

Funding Information:
This work was supported by a doctoral fellowship (11B0519N to J.M.), a postdoctoral fellowship (12P9818N to E.G), grants (G0C7118N and G0D8220N to A.A.) from the Research Foundation-Flanders (FWO-Vlaanderen), and a postdoctoral fellowship (PDM/20/ 118 to J.M.) from the KU Leuven Research Fund. The Switch Laboratory was supported by the Flanders institute for biotechnology (VIB), the University of Leuven and its Industrieel Onderzoeksfonds, and the Funds for Scientific Research Flanders (FWO).

Publisher Copyright:
© 2021 Mortier et al.


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