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Updated: Feb 2, 2026

Exploring Biomolecular Interaction Between the Molecular Chaperone Hsp90 and Its Client Protein Kinase Cdc37 using Field-Effect Biosensing Technology
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Heterologous Hsp90 promotes phenotypic diversity through network evolution.

Tracy Chih-Ting Koubkova-Yu1,2,3, Jung-Chi Chao2, Jun-Yi Leu1,2,4

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Network hubs like heat shock protein 90 (Hsp90) are evolvable. Replacing yeast Hsp90 with a divergent ortholog enabled adaptation and increased phenotypic diversity through beneficial mutations.

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Genetics

Background:

  • Gene networks integrate cellular signals and reactions via network hubs.
  • The evolvability of network hubs and their impact on long-term evolution are not well understood.
  • Heat shock protein 90 (Hsp90) is a crucial hub in proteostasis networks.

Purpose of the Study:

  • To investigate the evolvability of network hubs using Hsp90 as a model.
  • To determine how alterations in Hsp90 affect long-term evolutionary trajectories.
  • To explore the adaptive potential and phenotypic variation arising from heterologous Hsp90.

Main Methods:

  • Replaced native Saccharomyces cerevisiae Hsp90 with the ortholog from Yarrowia lipolytica.
  • Subjected cells with heterologous Hsp90 to laboratory evolution.
  • Analyzed phenotypic variation and identified beneficial mutations in evolved strains.

Main Results:

  • The Yarrowia lipolytica Hsp90 conferred improved growth in hypersaline conditions but reduced growth elsewhere, indicating functional divergence.
  • Laboratory evolution of Hsp90-carrying yeast cells revealed a broader range of phenotypic variation compared to wild-type.
  • Beneficial mutations were pleiotropic and affected multiple pathways, enabling adaptation to heterologous Hsp90.

Conclusions:

  • Cells can adapt to a heterologous Hsp90 by modifying various subnetworks.
  • Adaptation to a foreign Hsp90 facilitates the evolution of novel phenotypic diversity.
  • Network hubs, like Hsp90, are evolvable and can drive significant adaptive evolution.