- Open Access
The Rabs: A family at the root of metazoan evolution
© Stenmark; licensee BioMed Central Ltd. 2012
- Received: 27 July 2012
- Accepted: 1 August 2012
- Published: 8 August 2012
Eukaryotic cells are distinguished by their compartmentalization into membrane-enclosed organelles that exchange membranes and content in a highly ordered manner. Central in defining membrane identity are the Rabs, a large family of small GTPases that localize to distinct membranes and recruit specific regulators of membrane traffic. Two recent papers, including one by Klöpper et al. in BMC Biology, present phylogenomic evidence that the Rab repertoire was established very early in eukaryotic evolution, and correlates with interspecies variations in organelles.
See research article http://0-www.biomedcentral.com.brum.beds.ac.uk/1741-7007/10/71
- Membrane Traffic
- Eukaryotic Evolution
- Last Eukaryotic Common Ancestor
- Distinct Membrane
- Eukaryotic Common Ancestor
The era of whole-genome sequencing has offered new avenues for studying evolution at the molecular level, and Klöpper et al. took advantage of publicly available information on genome projects for as many as 384 different species, plus more than 200 species for which sufficient sequence information is known in other ways. Identifying Rabs by bioinformatics is no trivial task, however, since different Rabs show only regional sequence similarities and there are several hypervariable sequences . Adding to this complexity, other small GTPases show partial sequence similarity to Rabs, and it is difficult to sort out whether borderline cases represent genuine Rabs or not. The authors therefore started with a limited set of sequences (about 500 from 21 species) and used a hidden Markov model (a mathematical model favored by many bioinformaticists for comparing sequences in a relatively unbiased manner) in order to extract a core Rab motif that was used to screen the larger sample set, which contained more than 7,600 sequences from Rabs representing all major eukaryotic phyla. Out of this extensive analysis the authors identified a set of 20 basic Rab types, and by testing several hypotheses for the placement of the LECA in the root of the eukaryotic tree of life, the authors concluded that the LECA is most likely to have contained all these 20 Rabs. This is a surprisingly high number, but it correlates well with a recent study that used a smaller query set and a somewhat different methodology, and which estimated the number of different Rabs in the LECA to be up to 23 . The two studies thus agree that the Rab repertoire developed at a very early point in eukaryotic history.
When comparing the Rab repertoires of different species, it is conspicuous that some Rabs have been selectively lost during evolution of various species whereas others have expanded and diversified [5, 6]. For instance, a large number of new Rabs in group I have appeared in metazoans, which may reflect the fact that metazoans are multicellular and contain polarized cells, which requires a diversified set of exocytic routes . In fact, the gains and losses of Rabs can to a large extent be correlated with the numbers and types of organelles in the various species, a correlation that has not been found for other regulators of membrane traffic such as coat proteins, vesicle tethers and proteins directly involved in membrane fusion . This opens the possibility that gains, diversifications and losses of Rabs may have been the driving forces for organelle plasticity during evolution. Given the importance of organelle plasticity for species diversification and evolution, the recent findings should place Rabs among the favorite proteins for evolutionary biologists.
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