Abstract
The evolution of signal transduction pathways is constrained by the requirements of signal fidelity, yet flexibility is necessary to allow pathway remodeling in response to environmental challenges. A detailed understanding of how flexibility and constraint shape bacterial two component signaling systems is emerging, but how new signal transduction architectures arise remains unclear. Here, we investigate pathway remodeling using the Firmicute sporulation initiation (Spo0) pathway as a model. The present-day Spo0 pathways in Bacilli and Clostridia share common ancestry, but possess different architectures. In Clostridium acetobutylicum, sensor kinases directly phosphorylate Spo0A, the master regulator of sporulation. In Bacillus subtilis, Spo0A is activated via a four-protein phosphorelay. The current view favors an ancestral direct phosphorylation architecture, with the phosphorelay emerging in the Bacillar lineage. Our results reject this hypothesis. Our analysis of 84 broadly distributed Firmicute genomes predicts phosphorelays in numerous Clostridia, contrary to the expectation that the Spo0 phosphorelay is unique to Bacilli. Our experimental verification of a functional Spo0 phosphorelay encoded by Desulfotomaculum acetoxidans (Class Clostridia) further supports functional phosphorelays in Clostridia, which strongly suggests that the ancestral Spo0 pathway was a phosphorelay. Cross complementation assays between Bacillar and Clostridial phosphorelays demonstrate conservation of interaction specificity since their divergence over 2.7 BYA. Further, the distribution of direct phosphorylation Spo0 pathways is patchy, suggesting multiple, independent instances of remodeling from phosphorelay to direct phosphorylation. We provide evidence that these transitions are likely the result of changes in sporulation kinase specificity or acquisition of a sensor kinase with specificity for Spo0A, which is remarkably conserved in both architectures. We conclude that flexible encoding of interaction specificity, a phenotype that is only intermittently essential, and the recruitment of kinases to recognize novel environmental signals resulted in a consistent and repeated pattern of remodeling of the Spo0 pathway.
Highlights
Responses to changing environmental conditions are mediated by signal transduction pathways that recognize a signal, convey that signal into the cell, and initiate an appropriate cellular response
The Firmicute sporulation initiation (Spo0) pathway is a compelling example of a pathway with a circuit diagram that has changed over the course of evolution
In Bacillus subtilis, Spo0A is activated indirectly via a four-protein phosphorelay. These early observations suggested that the ancestral Spo0A was directly phosphorylated by a kinase in the earliest spore-former and that the Spo0 phosphorelay arose later in Bacilli via gain of additional proteins and interactions
Summary
Responses to changing environmental conditions are mediated by signal transduction pathways that recognize a signal, convey that signal into the cell, and initiate an appropriate cellular response. Two-component signaling systems, typically comprised of a histidine kinase (HK) and a cognate response regulator (RR), are a primary mechanism of environmental response (Fig 1A). Signal recognition by the N-terminal sensor region of the HK leads to the autophosphorylation of a conserved histidine residue in the so-called HisKA domain by the catalytic (HK_CA) domain. The signal is transduced by phosphotransfer from the autophosphorylated HK to a conserved aspartate residue in the N-terminal receiver (REC) domain of the RR [1]. Phosphorylation of the REC domain activates the C-terminal output domain of the RR, initiating a response to the recognized signal. Bacteria typically encode 20 to 30 two-component signaling pathways per genome [2]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call