Two-component systems (TCSs) are a large family of signalling pathways characterized by the successive transfer of phosphoryl groups between the histidine and aspartate residues of paired histidine kinase and response regulator proteins. With the availability of genome sequences for four genera of myxobacteria it has become possible to assess the genomic complements of myxobacterial TCS genes and to characterize features of their organization and evolutionary heritage. In this study we have compiled lists of the TCS genes within myxobacterial genomes and characterized their domain architecture, gene organization and evolutionary relationships. In order to provide an appropriate context for our conclusions, where possible we have compared myxobacterial TCSs with those found in 316 other completely sequenced bacteria. Myxobacteria have the largest number of TCSs of any organisms. An unusually low proportion of TCS genes are paired in myxobacterial genomes, and myxobacterial histidine kinases also seem to sense internal signals to an unusual degree. Phylogenetic evidence has allowed us to suggest homologous relationships of proteins across the myxobacteria, and it appears that myxobacterial TCS evolution has been dominated by duplications, gene rearrangements and changes in sensory domain complements. The systematic classification of the TCS proteins of the myxobacteria presented here should also provide a framework for future experimental studies on two-component regulation in these organisms.
ApplebyJ. L.,
ParkinJ. S.,
BourretR. B.1996; Signal transduction via the multi-step phosphorelay: not necessarily a road less traveled. Cell 86:845–848
BurbulysD.,
TrachK. A.,
HochJ. A.1991; The initiation of sporulation in Bacillus subtilis is controlled by a multicomponent phosphorelay. Cell 64:545–552
CaberoyN. B.,
WelchR. D.,
JakobsenJ. S.,
SlaterS. C.,
GarzaA. G.2003; Global mutational analysis of NtrC-like transcriptional activators in Myxococcus xanthus : identifying activator mutants defective for motility and fruiting body development. J Bacteriol 185:6083–6094
CockP. J. A.,
WhitworthD. E.2007a; Evolution of gene overlaps: relative reading frame bias in prokaryotic two-component system genes. J Mol Evol 64:457–462
CockP. J. A.,
WhitworthD. E.2007b; Evolution of prokaryotic two-component system signaling pathways: gene fusions and fissions. Mol Biol Evol 24:2355–2357
EllehaugeE.,
Norregaard-MadsenM.,
Søgaard-AndersenL.1998; The FruA signal transduction protein provides a checkpoint for the temporal co-ordination of inter-cellular signals in Myxococcus xanthus development. Mol Microbiol 30:807–817
GalperinM. Y.2005; A census of membrane-bound and intracellular signal transduction proteins in bacteria: bacterial IQ, extroverts and introverts. BMC Microbiol 5:35
GerthK.,
PradellaS.,
PerlovaO.,
BeyerS.,
MullerR.2003; Myxobacteria: proficient producers of novel natural products with various biological activities – past and future biotechnological aspects with the focus on the genus Sorangium . J Biotechnol 106:233–253
GoldmanB. S.,
NiermanW. C.,
KaiserD.,
SlaterS. C.,
DurkinA. S.,
EisenJ. A.,
RonningC. M.,
BarbazukW. B.,
BlanchardM.other authors2006; Evolution of sensory complexity recorded in a myxobacterial genome. Proc Natl Acad Sci U S A 103:15200–15205
GronewaldT. M. A.,
KaiserD.2001; The act operon controls the level and time of C-signal production for Myxococcus xanthus development. Mol Microbiol 40:744–756
HiggsP. I.,
ChoK.,
WhitworthD. E.,
EvansL. S.,
ZusmanD. R.2005; Four unusual two-component signal transduction homologs, RedC to RedF, are necessary for timely development in Myxococcus xanthus . J Bacteriol 187:8191–8195
HutchingsM. I.,
HoskissonP. A.,
ChandraG.,
ButtnerM. J.2004; Sensing and responding to extracellular signals? Analysis of the sensor kinases and response regulators of Streptomyces coelicolor A3(2. Microbiology 150:2795–2806
JelsbakL.,
GivskovM.,
KaiserD.2005; Enhancer-binding proteins with a forkhead-associated domain and the σ 54 regulon in Myxococcus xanthus fruiting body development. Proc Natl Acad Sci U S A 102:3010–3015
MizunoT.,
KanekoT.,
TabataS.1996; Compilation of all genes encoding bacterial two-component signal transducers in the genome of the cyanobacterium, Synechocystis sp. strain PCC 6803. DNA Res 3:407–414
Peña-SandovalG. R.,
KwonO.,
GeorgellisD.2005; Requirement of the receiver and phosphotransfer domains of ArcB for efficient dephosphorylation of phosphorylated ArcA in vivo. J Bacteriol 187:3267–3272
RasmussenA. A.,
PorterS. L.,
ArmitageJ. P.,
Sogaard-AndersenL.2005; Coupling of multicellular morphogenesis and cellular differentiation by an unusual hybrid histidine protein kinase in Myxococcus xanthus . Mol Microbiol 56:1358–1372
RasmussenA. A.,
Wegener-FeldbruggeS.,
PorterS. L.,
ArmitageJ. P.,
Sogaard-AndersenL.2006; Four signalling domains in the hybrid histidine protein kinase RodK of Myxococcus xanthus are required for activity. Mol Microbiol 60:525–534
SanfordR. A.,
ColeJ. R.,
TiedjeJ. M.2002; Characterization and description of Anaeromyxobacter dehalogenans gen. nov., sp. nov., an aryl-halorespiring facultative anaerobic myxobacterium. Appl Environ Microbiol 68:893–900
SonnhammerE. L.,
von HeijneG.,
KroghA.1998; A hidden Markov model for predicting transmembrane helices in protein sequences. Proc Int Conf Intell Syst Mol Biol 6:175–182
ThompsonJ. D.,
HigginsD. G.,
GibsonT. J.1994; CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680
TrudeauK. G.,
WardM. J.,
ZusmanD. R.1996; Identification and characterization of FrzZ, a novel response regulator necessary for swarming and fruiting-body formation in Myxococcus xanthus . Mol Microbiol 20:645–655
VosM.,
VelicerG. J.2006; Genetic population structure of the soil bacterium Myxococcus xanthus at the centimeter scale. Appl Environ Microbiol 72:3615–3625
WardM. J.,
LewH.,
ZusmanD. R.2000; Social motility in Myxococcus xanthus requires FrzS, a protein with an extensive coiled-coil domain. Mol Microbiol 37:1357–1371
WhitworthD. E.2007Myxobacteria: Multicellularity and Differentiation Washington, DC: American Society for Microbiology;
WhitworthD. E.,
CockP. J. A.2007; Myxobacterial two-component systems. In Myxobacteria: Multicellularity and Differentiation pp 169–189 Edited by
WhitworthD. E.
Washington, DC: American Society for Microbiology;