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PLoS Genet. 2015 Aug 20;11(8):e1005460. doi: 10.1371/journal.pgen.1005460. eCollection 2015 Aug.

Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway.

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Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, CNRS Aix-Marseille University UMR 7283, Marseille, France.
Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, CNRS Universités de Montpellier II et I, UMR 5235, case 107, Montpellier, France.
Université de Lyon, Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France.


Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz) coordinates the activity of two separate motility systems (the A- and S-motility systems), promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways.

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