Evolution and diversity of the Ras superfamily of small GTPases in prokaryotes

Genome Biol Evol. 2014 Dec 4;7(1):57-70. doi: 10.1093/gbe/evu264.


The Ras superfamily of small GTPases are single domain nucleotide-dependent molecular switches that act as highly tuned regulators of complex signal transduction pathways. Originally identified in eukaryotes for their roles in fundamental cellular processes including proliferation, motility, polarity, nuclear transport, and vesicle transport, recent studies have revealed that single domain GTPases also control complex functions such as cell polarity, motility, predation, development and antibiotic resistance in bacteria. Here, we used a computational genomics approach to understand the abundance, diversity, and evolution of small GTPases in prokaryotes. We collected 520 small GTPase sequences present in 17% of 1,611 prokaryotic genomes analyzed that cover diverse lineages. We identified two discrete families of small GTPases in prokaryotes that show evidence of three distinct catalytic mechanisms. The MglA family includes MglA homologs, which are typically associated with the MglB GTPase activating protein, whereas members of the Rup (Ras superfamily GTPase of unknown function in prokaryotes) family are not predicted to interact with MglB homologs. System classification and genome context analyses support the involvement of small GTPases in diverse prokaryotic signal transduction pathways including two component systems, laying the foundation for future experimental characterization of these proteins. Phylogenetic analysis of prokaryotic and eukaryotic GTPases supports that the last universal common ancestor contained ancestral MglA and Rup family members. We propose that the MglA family was lost from the ancestral eukaryote and that the Ras superfamily members in extant eukaryotes are the result of vertical and horizontal gene transfer events of ancestral Rup GTPases.

Keywords: GTPase-activating protein; MglA; Ras; evolution; signal transduction; small GTPase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics*
  • Biological Evolution*
  • Cell Movement / genetics
  • Cell Polarity / genetics
  • Computational Biology
  • Drug Resistance, Microbial / genetics
  • Genomics
  • Monomeric GTP-Binding Proteins / genetics*
  • Multigene Family
  • Phylogeny
  • Prokaryotic Cells*
  • Signal Transduction / genetics


  • Monomeric GTP-Binding Proteins