Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations

Mol Biol Evol. 2015 Oct;32(10):2681-93. doi: 10.1093/molbev/msv144. Epub 2015 Jun 27.


Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherichia coli expressing high levels of the essential chaperonin GroEL. GroEL is abundantly present in bacteria, particularly in bacteria with large loads of deleterious mutations, suggesting its role in mutational buffering. We show that groEL overexpression is costly to large populations evolving in the laboratory, leading to groE expression decline within 66 generations. In contrast, populations evolving under the strong genetic drift characteristic of endosymbiotic bacteria avoid extinction or can be rescued in the presence of abundant GroEL. Genomes resequenced from cells evolved under strong genetic drift exhibited significantly higher tolerance to deleterious mutations at high GroEL levels than at native levels, revealing that GroEL is buffering mutations in these cells. GroEL buffered mutations in a highly diverse set of proteins that interact with the environment, including substrate and ion membrane transporters, hinting at its role in ecological diversification. Our results reveal the fitness trade-offs of mutational buffering and how genetic variation is maintained in populations.

Keywords: Escherichia coli; GroEL; experimental evolution; mutational buffering.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Chaperonin 60 / genetics*
  • Chaperonin 60 / metabolism
  • Directed Molecular Evolution
  • Escherichia coli / genetics*
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Genetic Drift
  • Genetic Fitness*
  • Mutation / genetics*
  • Operon / genetics
  • Subcellular Fractions / metabolism


  • Chaperonin 60