"The diversity of cell cycle regulation in alpha proteobacteria: a comparative analysis"

In the bacterium Caulobacter crescentus, CtrA sits at the center of a complex regulatory system controlling DNA replication, cell division, and morphogenesis of polar structures and therefore is considered the master regulator of cell cycle progression. CtrA is a response regulator whose activity is modulated by phosphorylation, proteolysis and transcriptional control. When CtrA is phosphorylated it binds specific DNA sequences and can repress or activate expression of genes involved in many aspects of the cell cycle and it can silence the origin of replication. Although this circuitry regulating CtrA is known in molecular details in Caulobacter, its conservation and function in other alpha proteobacteria is still poorly understood.

Here we systematically analyzed the organization of factors involved in the regulation of CtrA in genomes of alpha proteobacteria. In particular we looked for orthologous genes of the Caulobacter ones and also we predicted the CtrA regulons in all sequenced alphas. The cell cycle regulation architecture has been reconstructed in alpha proteobacteria revealing a high diversification. However an evolutionary model is proposed where ancient members of alpha-proteobacteria possessed a variety of arrangements of all regulatory modules found in Caulobacter.

Two schemes then derived from this ancestral situation: a complex circuit similar to the Caulobacter one and a simpler one found in Rhodobacterales. Interestingly both organizations reveal a circuit with two interconnected oscillators that was also proposed for eukaryotes.