Evolutionary history expands the range of signaling interactions in hybrid multikinase networks

Authors Organisations
  • Philippe Ortet(Author)
    Aix-Marseille University
  • Sylvain Fochesato(Author)
    Aix-Marseille University
  • Anne-Florence Bitbol(Author)
    Sorbonne University
    Swiss Federal Institute of Technology in Lausanne
  • David Whitworth(Author)
  • David Lalaouna(Author)
    Aix-Marseille University
    University of Strasbourg
  • Catherine Santaella(Author)
    Aix-Marseille University
  • Thierry Heulin(Author)
    Aix-Marseille University
  • Wafa Achouak(Author)
    Aix-Marseille University
  • Mohamed Barakat(Author)
    Aix-Marseille University
Type Article
Original languageEnglish
Pages (from-to)11763
Number of pages12
JournalScientific Reports
Issue number1
Early online date03 Jun 2021
Publication statusE-pub ahead of print - 03 Jun 2021
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Abstract: Two-component systems (TCSs) are ubiquitous signaling pathways, typically comprising a sensory histidine kinase (HK) and a response regulator, which communicate via intermolecular kinase-to-receiver domain phosphotransfer. Hybrid HKs constitute non-canonical TCS signaling pathways, with transmitter and receiver domains within a single protein communicating via intramolecular phosphotransfer. Here, we report how evolutionary relationships between hybrid HKs can be used as predictors of potential intermolecular and intramolecular interactions (‘phylogenetic promiscuity’). We used domain-swap genes chimeras to investigate the specificity of phosphotransfer within hybrid HKs of the GacS–GacA multikinase network of Pseudomonas brassicacearum. The receiver domain of GacS was replaced with those from nine donor hybrid HKs. Three chimeras with receivers from other hybrid HKs demonstrated correct functioning through complementation of a gacS mutant, which was dependent on strains having a functional gacA. Formation of functional chimeras was predictable on the basis of evolutionary heritage, and raises the possibility that HKs sharing a common ancestor with GacS might remain components of the contemporary GacS network. The results also demonstrate that understanding the evolutionary heritage of signaling domains in sophisticated networks allows their rational rewiring by simple domain transplantation, with implications for the creation of designer networks and inference of functional interactions.


  • Article, /631/326, /631/326/41, /631/326/41/2529, /631/114, /631/114/2114, article