title: The diversity and evolution of cell cycle regulation in alpha-proteobacteria: a comparative genomic analysis.
abstract: BACKGROUND
  In the bacterium Caulobacter crescentus, CtrA coordinates DNA replication, cell division, and polar morphogenesis and is considered the cell cycle master regulator. CtrA activity varies during cell cycle progression and is modulated by phosphorylation, proteolysis and transcriptional control. In a phosphorylated state, CtrA binds specific DNA sequences, regulates the expression of genes involved in cell cycle progression and silences the origin of replication. Although the circuitry regulating CtrA is known in molecular detail in Caulobacter, its conservation and functionality in the other alpha-proteobacteria are still poorly understood.
  
  
  RESULTS
  Orthologs of Caulobacter factors involved in the regulation of CtrA were systematically scanned in genomes of alpha-proteobacteria. In particular, orthologous genes of the divL-cckA-chpT-ctrA phosphorelay, the divJ-pleC-divK two-component system, the cpdR-rcdA-clpPX proteolysis system, the methyltransferase ccrM and transcriptional regulators dnaA and gcrA were identified in representative genomes of alpha-proteobacteria. CtrA, DnaA and GcrA binding sites and CcrM putative methylation sites were predicted in promoter regions of all these factors and functions controlled by CtrA in all alphas were predicted.
  
  
  CONCLUSIONS
  The regulatory cell cycle architecture was identified in all representative alpha-proteobacteria, revealing a high diversification of circuits but also a conservation of logical features. An evolutionary model was proposed where ancient alphas already possessed all modules found in Caulobacter arranged in a variety of connections. Two schemes appeared to evolve: a complex circuit in Caulobacterales and Rhizobiales and a simpler one found in Rhodobacterales.
authors.affiliation: Department of Evolutionary Biology, University of Florence, via Romana, 17, Florence, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brilli
authors.forename: Marco
authors.initials: M
authors.lastname: Fondi
authors.forename: Renato
authors.initials: R
authors.lastname: Fani
authors.forename: Alessio
authors.initials: A
authors.lastname: Mengoni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ferri
authors.forename: Marco
authors.initials: M
authors.lastname: Bazzicalupo
authors.forename: Emanuele G
authors.initials: EG
authors.lastname: Biondi
mesh_terms: D020561:Alphaproteobacteria / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D001665:Binding Sites; D016935:Caulobacter crescentus / Q000235:genetics*; D002453:Cell Cycle; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D023281:Genomics; D008957:Models, Genetic; D010766:Phosphorylation; D010802:Phylogeny; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C097706:CtrA protein, Caulobacter; D004268:DNA-Binding Proteins; D014157:Transcription Factors