Comparative Genomic Analysis of Multi-Subunit Tethering Complexes Demonstrates an Ancient Pan-Eukaryotic Complement and Sculpting in Apicomplexa
Open Access
- 27 September 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (9), e76278
- https://doi.org/10.1371/journal.pone.0076278
Abstract
Apicomplexa are obligate intracellular parasites that cause tremendous disease burden world-wide. They utilize a set of specialized secretory organelles in their invasive process that require delivery of components for their biogenesis and function, yet the precise mechanisms underpinning such processes remain unclear. One set of potentially important components is the multi-subunit tethering complexes (MTCs), factors increasingly implicated in all aspects of vesicle-target interactions. Prompted by the results of previous studies indicating a loss of membrane trafficking factors in Apicomplexa, we undertook a bioinformatic analysis of MTC conservation. Building on knowledge of the ancient presence of most MTC proteins, we demonstrate the near complete retention of MTCs in the newly available genomes for Guillardia theta and Bigelowiella natans. The latter is a key taxonomic sampling point as a basal sister taxa to the group including Apicomplexa. We also demonstrate an ancient origin of the CORVET complex subunits Vps8 and Vps3, as well as the TRAPPII subunit Tca17. Having established that the lineage leading to Apicomplexa did at one point possess the complete eukaryotic complement of MTC components, we undertook a deeper taxonomic investigation in twelve apicomplexan genomes. We observed excellent conservation of the VpsC core of the HOPS and CORVET complexes, as well as the core TRAPP subunits, but sparse conservation of TRAPPII, COG, Dsl1, and HOPS/CORVET-specific subunits. However, those subunits that we did identify appear to be expressed with similar patterns to the fully conserved MTC proteins, suggesting that they may function as minimal complexes or with analogous partners. Strikingly, we failed to identify any subunits of the exocyst complex in all twelve apicomplexan genomes, as well as the dinoflagellate Perkinsus marinus. Overall, we demonstrate reduction of MTCs in Apicomplexa and their ancestors, consistent with modification during, and possibly pre-dating, the move from free-living marine algae to deadly human parasites.This publication has 114 references indexed in Scilit:
- Cryptic organelle homology in apicomplexan parasites: insights from evolutionary cell biologyCurrent Opinion in Microbiology, 2013
- An automated graphics tool for comparative genomics: the Coulson plot generatorBMC Bioinformatics, 2013
- Evolution of apicomplexan secretory organellesInternational Journal for Parasitology, 2012
- A Structure-Based Mechanism for Vesicle Capture by the Multisubunit Tethering Complex Dsl1Cell, 2009
- Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complexNature Structural & Molecular Biology, 2009
- The TRAPP Complex: Insights into its Architecture and FunctionTraffic, 2008
- Requirement of the Human GARP Complex for Mannose 6-phosphate-receptor-dependent Sorting of Cathepsin D to LysosomesMolecular Biology of the Cell, 2008
- RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed modelsBioinformatics, 2006
- Cytoskeletal Components of an Invasion Machine—The Apical Complex of Toxoplasma gondiiPLoS Pathogens, 2006
- The Plasmodium falciparum sexual development transcriptome: A microarray analysis using ontology-based pattern identificationMolecular and Biochemical Parasitology, 2005