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

Abstract

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.

Genome-Wide Transcriptional Dynamics in the Companion Bacterial Symbionts of the Glassy-Winged Sharpshooter (Cicadellidae: Homalodisca vitripennis) Reveal Differential Gene Expression in Bacteria Occupying Multiple Host Organs

“…One apparent coping mechanism is the constitutive overexpression of protein chaperonins and heat shock proteins by symbionts. Chaperonins in free-living bacteria buffer enzyme function against the effects of environmental extremes, oxidative stress, and genetic drift, which are major forces shaping symbiont genome evolution ( Williams et al 2010 ; McCutcheon and Moran 2012 ; Sabater-Muñoz et al 2015 ). In bacterial symbionts, chaperonins likely aid in the proper folding of proteins debilitated by the accumulation of deleterious mutations ( Moran 1996 ; Fares et al 2004 ; Kupper et al 2014 ).…”

“…Nevertheless, high constitutive expression of GroESL is likely costly to hosts. It is known to be highly expressed as protein in pea aphids, requiring extensive cellular resources ( Baumann et al 1996 ; Sabater-Muñoz et al 2015 ). Furthermore, it may also impose ecological constraints on plant–insect interactions.…”

Dissecting genome reduction and trait loss in insect endosymbionts

“…This is the case for the chaperone GroEL, a protein that is overexpressed in endosymbiotic bacteria and seems to participate in the correct folding of many damaged proteins, thus buffering the effect of slightly deleterious mutations . In fact, a number of elegant experiments carried out in Escherichia coli have shown that overexpression of GroEL in bacteria evolving under continuous bottleneck, and thus with a strong genetic drift, can avoid extinction or rescue bacterial cells …”

Evolution of Chaperonin Gene Duplication in Stigonematalean Cyanobacteria (Subsection V)

“…Moreover, accumulating evidence suggests that the function of chaperones has important consequences for robustness (Queitsch et al. 2002) and adaptation to high mutational load (Sabater-Muñoz et al. 2015).…”