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

Understanding the principles underlying the plasticity of signal transduction networks is fun-damental to decipher the functioning of living cells. InMyxococcus 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 evolu-tion-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 dupli-cation 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 increas-ing 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 regula-tor 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 signa