Distribution and evolution of multiple-step phosphorelay in prokaryotes: lateral domain recruitment involved in the formation of hybrid-type histidine kinases

Microbiology (Reading). 2005 Jul;151(Pt 7):2159-2173. doi: 10.1099/mic.0.27987-0.


Although most two-component signal transduction systems use a simple phosphotransfer pathway from one histidine kinase (HK) to one response regulator (RR), a multiple-step phosphorelay involving a phosphotransfer scheme of His-Asp-His-Asp was also discovered. Central to this multiple-step-type signal transduction pathway are a hybrid-type HK, containing both an HK domain and an RR receiver domain in a single protein, and a histidine-containing phosphotransfer (HPT) that can exist either as a domain in hybrid-type HKs or as a separate protein. Although multiple-step phosphorelay systems are predominant in eukaryotes, it has been previously suggested that they are less common in prokaryotes. In this study, it was found that putative hybrid-type HKs were present in 56 of 156 complete prokaryotic genomes, indicating that multiple-step phosphorelay systems are more common in prokaryotes than previously appreciated. Large expansions of hybrid-type HKs were observed in 26 prokaryotic species, including photosynthetic cyanobacteria such as Nostoc sp. PCC 7120, and several pathogenic bacteria such as Coxiella burnetii. Phylogenetic analysis indicated that there was no common ancestor for hybrid-type HKs, and their origin and expansion was achieved by lateral recruitment of a receiver domain into an HK molecule and then duplication as one unit. Lateral recruitment of additional sensory domains such as PAS was also evident. HPT domains or proteins were identified in 32 of the genomes with hybrid-type HKs; however, no significant gene expansion was observed for HPTs even in a genome with a large number of hybrid-type HKs. In addition, fewer HPTs than hybrid-type HKs were identified in all prokaryotic genomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Genome, Bacterial*
  • Histidine / metabolism*
  • Phosphorylation
  • Protein Kinases / genetics*
  • Protein Kinases / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology


  • Histidine
  • Protein Kinases