title: Evolution of Tre-2/Bub2/Cdc16 (TBC) Rab GTPase-activating proteins.
abstract: Rab GTPases serve as major control elements in the coordination and definition of specific trafficking steps and intracellular compartments. Rab activity is modulated in part by GTPase-activating proteins (GAPs), and many RabGAPs share a Tre-2/Bub2/Cdc16 (TBC)-domain architecture, although the majority of TBC proteins are poorly characterized. We reconstruct the evolutionary history of the TBC family using ScrollSaw, a method for the phylogenetic analysis of pan-eukaryotic data sets, and find a sophisticated, ancient TBC complement of at least 10 members. Significantly, the TBC complement is nearly always smaller than the Rab cohort in any individual genome but also suggests Rab/TBC coevolution. Further, TBC-domain architecture has been well conserved in modern eukaryotes. The reconstruction also shows conservation of ancestral TBC subfamilies, continuing evolution of new TBCs, and frequent secondary losses. These patterns give additional insights into the sculpting of the endomembrane system.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
authors.forename: Carme
authors.initials: C
authors.lastname: Gabernet-Castello
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: O'Reilly
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.forename: Mark C
authors.initials: MC
authors.lastname: Field
mesh_terms: D000818:Animals; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics*; D019143:Evolution, Molecular; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D023281:Genomics; D006801:Humans; D016366:Open Reading Frames; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; C577395:CDC16 protein, human; D020690:GTPase-Activating Proteins; D011518:Proto-Oncogene Proteins; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; C518767:TBC1D4 protein, human; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase