Journal Article


Mario A Fares
Andreas Wagner
David Alvarez-Ponce
Víctor Berlanga
Roser Montagud-Martínez
Beatriz Sabater-Muñoz
José Aguilar-Rodríguez



heat shock proteins protein structure molecular chaperone escherichia coli protein function robustness molecular chaperones source

The molecular chaperone DnaK is a source of mutational robustness. (2016)

Abstract Molecular chaperones, also known as heat-shock proteins, refold misfolded proteins and help other proteins reach their native conformation. Thanks to these abilities, some chaperones, such as the Hsp90 protein or the chaperonin GroEL, can buffer the deleterious phenotypic effects of mutations that alter protein structure and function. Hsp70 chaperones use a chaperoning mechanism different from that of Hsp90 and GroEL, and it is not known whether they can also buffer mutations. Here, we show that they can. To this end, we performed a mutation accumulation experiment in Escherichia coli, followed by whole-genome resequencing. Overexpression of the Hsp70 chaperone DnaK helps cells cope with mutational load and completely avoid the extinctions we observe in lineages evolving without chaperone overproduction. Additionally, our sequence data show that DnaK overexpression increases mutational robustness, the tolerance of its clients to nonsynonymous nucleotide substitutions. We also show that this elevated mutational buffering translates into differences in evolutionary rates on intermediate and long evolutionary time scales. Specifically, we studied the evolutionary rates of DnaK clients using the genomes of E. coli, Salmonella enterica, and 83 other gamma-proteobacteria. We find that clients that interact strongly with DnaK evolve faster than weakly interacting clients. Our results imply that all three major chaperone classes can buffer mutations and affect protein evolution. They illustrate how an individual protein like a chaperone can have a disproportionate effect on the evolution of a proteome.
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Full list of authors on original publication

Mario A Fares, Andreas Wagner, David Alvarez-Ponce, Víctor Berlanga, Roser Montagud-Martínez, Beatriz Sabater-Muñoz, José Aguilar-Rodríguez

Experts in our system

Mario Ali Fares
Trinity College Dublin
Total Publications: 43
Beatriz Sabater-Muñoz
Trinity College Dublin
Total Publications: 3