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Sculpting the endomembrane system in deep time: high resolution phylogenetics of Rab GTPases
Marek Elias, Andrew Brighouse, Carme Gabernet-Castello, Mark C. Field, Joel B. Dacks


The presence of a nucleus and other membrane-bounded intracellular compartments is the defining feature of eukaryotic cells. Endosymbiosis accounts for the origins of mitochondria and plastids, but the evolutionary ancestry of the remaining cellular compartments is incompletely documented. Resolving the evolutionary history of organelle-identity encoding proteins within the endomembrane system is a necessity for unravelling the origins and diversification of the endogenously derived organelles. Comparative genomics reveals events after the last eukaryotic common ancestor (LECA), but resolution of events prior to LECA, and a full account of the intracellular compartments present in LECA, has proved elusive. We have devised and exploited a new phylogenetic strategy to reconstruct the history of the Rab GTPases, a key family of endomembrane-specificity proteins. Strikingly, we infer a remarkably sophisticated organellar composition for LECA, which we predict possessed as many as 23 Rab GTPases. This repertoire is significantly greater than that present in many modern organisms and unexpectedly indicates a major role for secondary loss in the evolutionary diversification of the endomembrane system. We have identified two Rab paralogues of unknown function but wide distribution, and thus presumably ancient nature; RabTitan and RTW. Furthermore, we show that many Rab paralogues emerged relatively suddenly during early metazoan evolution, which is in stark contrast to the lack of significant Rab family expansions at the onset of most other major eukaryotic groups. Finally, we reconstruct higher-order ancestral clades of Rabs primarily linked with endocytic and exocytic process, suggesting the presence of primordial Rabs associated with the establishment of those pathways and giving the deepest glimpse to date into pre-LECA history of the endomembrane system.


  • Funding

    The research was supported by the Czech Science Foundation [grant number P305/10/0205 to M.E.]; the Institute of Environmental Technologies [project registration number CZ.1.05/2.1.00/03.0100 to M.E.]; a Natural Sciences and Engineering Research Council of Canada Discovery Grant [grant number RPGIN 372638-09 to J.B.D.]; Alberta Innovates Technology Futures [grant number NFAO201000076 to J.B.D.]; and a Wellcome Trust program grant [grant number 082813 to M.C.F.]. Deposited in PMC for release after 6 months.

  • Supplementary material available online at

  • Accepted January 26, 2012.
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