Chaperone client proteins evolve slower than non-client proteins

Abstract

Chaperones are important molecular machinery that assists proteins to attain their native three-dimensional structure crucial for function. Earlier studies using experimental evolution showed that chaperones impose a relaxation of sequence constraints on their “client” proteins, which may lead to the fixation of slightly deleterious mutations on the latter. However, we hypothesized that such a phenomenon might be harmful to the organism in a natural physiological condition. In this study, we investigated the evolutionary rates of chaperone client and non-client proteins in five model organisms from both prokaryotic and eukaryotic lineages. Our study reveals a slower evolutionary rate of chaperone client proteins in all five organisms. Additionally, the slower folding rate and lower aggregation propensity of chaperone client proteins reveal that the chaperone may play an essential role in rescuing the slightly disadvantageous effects due to random mutations and subsequent protein misfolding. However, the fixation of such mutations is less likely to be selected in the natural population.

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Funding

The authors received financial assistance from the Bose Institute and Centre of Excellence in Bioinformatics.

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M.P.V., D.A., and S.C. designed the study. M.A.P. and S.C. performed the analysis. M.P.V., D.A., and S.C. drafted the manuscript. S.C. and T.C.G. completed the final version of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sandip Chakraborty or Tapash Chandra Ghosh.

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Victor, M.P., Acharya, D., Chakraborty, S. et al. Chaperone client proteins evolve slower than non-client proteins. Funct Integr Genomics 20, 621–631 (2020). https://doi.org/10.1007/s10142-020-00740-1

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Keywords

  • Chaperone
  • Chaperone client proteins
  • Evolutionary rate
  • Protein aggregation propensity
  • Protein folding rate