Seminar Series in Quantitative Life Sciences and Medicine

"Evolutionary rewiring of a bacterial signaling pathway"

Dannie Durand, Carnegie Mellon University
Tuesday October 9, 12-1pm
McIntyre Building, Room 1027

Survival in a changing world requires flexible signaling circuitry that can evolve in response to new environmental challenges. The Firmicute sporulation initiation (Spo0) pathway is a compelling example of signaling circuitry that has changed over evolution. In Clostridium acetobutylicum, the signal is passed directly from a sensor kinase to the activator of sporulation. In Bacillus subtilis, the signal is transmitted from the sensor through two intermediate proteins to the activator, in a so-called phosphorelay. What was the ancestral pathway architecture and how did evolution produce different circuit diagrams that control the same phenotype?

The current view is that the ancestral Spo0 pathway had the simpler two-protein architecture and that the four-protein phosphorelay arose later in Bacilli. Our analysis of 84 Firmicutes genomes challenges this hypothesis. We identified phosphorelays in many Clostridia, as well as Bacilli, consistent with a model wherein the ancestral pathway was a phosphorelay and the present-day two-protein pathway arose later through evolutionary rewiring. This model is further supported by in vitro phosphotransfer experiments in which replacing any Bacillar phosphorelay protein with the corresponding protein from a Clostridial phosphorelay results in a functional pathway. This implies that the molecular recognition signals that control interaction specificity in the Spo0 phosphorelay have not changed in the 2.7 billion years since the divergence of the Bacilli and the Clostridia. Finally, the phylogenetic distribution of two-protein Spo0 pathways is patchy, suggesting multiple, independent instances of rewiring from a four-protein phosphorelay to a two-protein pathway.