Evolution of vesicular transport in kinetoplastids: dynamics and novel gene products

The membrane trafficking system mediates delivery of macromolecules and metabolites to discrete intracellular compartments from their site of uptake or synthesis. For many pathogens the trafficking system has a special relevance as it is responsible for maintaining the host-pathogen interface, i.e., the cell surface. Both the surface and the underlying trafficking apparatus are intimately connected with immune evasion in many parasites including those belonging to the highly divergent order Kinetoplastida. Kinetoplastid parasites are etiological agents of several neglected tropical diseases such as African sleeping sickness, Chagas disease, and Leishmaniasis. Newly available sequences of many kinetoplastid genomes were used to reconstruct evolution of trafficking across this lineage, using three central paralogous trafficking families: Rabs, SNAREs and Rab-GAPs, which have defined roles in specific trafficking events. Further, proteomics was used to analyse a representative SNARE complex to explore compositional conservation between kinetoplastids and Opistokhonts. Overall there is little evidence for large scale expansions or contractions of these protein families, excluding a direct association with parasitism or changes to host range, host immunosophistication or transmission mechanisms. The data indicate a stepwise sculpting of the trafficking system where the large repertoire of the basal bodonids is mainly retained by the cruzi group, while extensive lossses characterise other lineages, particularly the African trypanosomes and phytomonads. Kinetoplastids possess several lineage-specific Rabs but all retain a core canonical Rab set; by contrast there is little novelty within the SNARE family even though certain canonical endosomal SNAREs appear to show a considerable degree of sequence divergence. Proteomics suggests that SNARE complex composition is largely conserved. The major changes in Rab and SNARE repertoires are associated with endosomal and late exocytic pathways, which is consistent with the considerable evolution of surface proteomes. Therefore, despite the absence of a transition per se associated with parasitism, adaptation of membrane trafficking is likely under active selection where it meets the host environment.The Gates Cambridge Scholarship Lundgren Research Award Philosophical Society Research Studentship Research - Wellcome Trus