title: The Molecular Chaperone DnaK Is a Source of Mutational Robustness.
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.
authors: Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland.
authors: José
authors: J
authors: Aguilar-Rodríguez
authors: Department of Abiotic Stress, Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), Valencia, Spain Department of Genetics, Smurfit Institute of Genetics, University of Dublin Trinity College Dublin, Dublin, Ireland.
authors: Beatriz
authors: B
authors: Sabater-Muñoz
authors: Department of Abiotic Stress, Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), Valencia, Spain.
authors: Roser
authors: R
authors: Montagud-Martínez
authors: Department of Abiotic Stress, Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), Valencia, Spain.
authors: Víctor
authors: V
authors: Berlanga
authors: Department of Biology, University of Nevada, Reno, Reno, Nevada, USA.
authors: David
authors: D
authors: Alvarez-Ponce
authors: Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland Swiss Institute of Bioinformatics, Lausanne, Switzerland Santa Fe Institute, Santa Fe, New Mexico, USA andreas.wagner@ieu.uzh.ch mfares@ibmcp.upv.es faresm@tcd.ie.
authors: Andreas
authors: A
authors: Wagner
authors: Department of Abiotic Stress, Instituto de Biología Molecular y Celular de Plantas (CSIC-UPV), Valencia, Spain Department of Genetics, Smurfit Institute of Genetics, University of Dublin Trinity College Dublin, Dublin, Ireland andreas.wagner@ieu.uzh.ch mfares@ibmcp.upv.es faresm@tcd.ie.
authors: Mario A
authors: MA
authors: Fares
mesh_terms: D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D059645:Mutation Rate; D017354:Point Mutation
chemical_list: D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; C063842:dnaK protein, E coli
keywords: DnaK; Escherichia coli; experimental evolution; molecular chaperones; mutational robustness; protein evolution