More than one way to build a flagellum: comparative genomics of parasitic protozoa

Briggs, L.; Davidge, Jacqueline; Wickstead, Bill; Ginger, Michael L.; Gull, Keith

doi:10.1016/j.cub.2004.07.041

Cited by 115 publications

(111 citation statements)

References 12 publications

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“…Wellknown examples of loss include de novo purine and tryptophan biosynthesis, polyU tails in plastid transcripts (47), and conserved eukaryotic components of flagellar transport (IFT20) (48) and endosomal sorting complexes (ESCRTs; Vsp24, Vsp27, and Vsp37A) (49). All of them are present in chrompodellids, confirming that their loss in the ancestor of apicomplexans coincides with the origin of parasitism (Fig.…”

Section: /Namentioning

confidence: 79%

Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Janouškovec

Tikhonenkov

Burki

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

181

189

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Apicomplexans are a major lineage of parasites, including causative agents of malaria and toxoplasmosis. How such highly adapted parasites evolved from free-living ancestors is poorly understood, particularly because they contain nonphotosynthetic plastids with which they have a complex metabolic dependency. Here, we examine the origin of apicomplexan parasitism by resolving the evolutionary distribution of several key characteristics in their closest free-living relatives, photosynthetic chromerids and predatory colpodellids. Using environmental sequence data, we describe the diversity of these apicomplexan-related lineages and select five species that represent this diversity for transcriptome sequencing. Phylogenomic analysis recovered a monophyletic lineage of chromerids and colpodellids as the sister group to apicomplexans, and a complex distribution of retention versus loss for photosynthesis, plastid genomes, and plastid organelles. Reconstructing the evolution of all plastid and cytosolic metabolic pathways related to apicomplexan plastid function revealed an ancient dependency on plastid isoprenoid biosynthesis, predating the divergence of apicomplexan and dinoflagellates. Similarly, plastid genome retention is strongly linked to the retention of two genes in the plastid genome, sufB and clpC, altogether suggesting a relatively simple model for plastid retention and loss. Lastly, we examine the broader distribution of a suite of molecular characteristics previously linked to the origins of apicomplexan parasitism and find that virtually all are present in their free-living relatives. The emergence of parasitism may not be driven by acquisition of novel components, but rather by loss and modification of the existing, conserved traits.A picomplexans are globally important parasites of humans and animals that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis). Their success as parasites rests on several highly specialized structures and systems that enable them to gain entry to and divide within cells or tissues of their hosts. These structures include the multimembrane pellicle, a relict nonphotosynthetic plastid (absent in Cryptosporidium), and the apical complex, which is made up of cytoskeletal and secretory elements (e.g., the conoid and rhoptries, respectively). Many specific characteristics of apicomplexans make attractive drug targets, and others may have played a key role in the origin of parasitism. Indeed, the question of apicomplexan origins has been of interest in general but is challenged by a paucity of comparable information from free-living relatives. Several apicomplexan relatives are known, some photosynthetic and others predatory (1, 2), but we lack a comprehensive understanding of their biology because they have either been discovered only recently, or are difficult to establish and maintain in culture. In general, photosynthetic apicomplexan relatives are referred to as chromerids (including Chromera and Vitrella) (1, 3) whereas predators...

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Section: /Namentioning

confidence: 79%

Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Janouškovec

Tikhonenkov

Burki

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

181

189

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“…This situation is by no means universal for all spermatozoa: for example, substantial amounts of two subunits of the heterotrimeric IFT kinesin II are present in the flagellum of mature spermatozoa in sea urchin and sand dollar (Henson et al, 1997). Third, IFT is absent and obviously not required for flagellum construction when it takes place in the cytoplasm, as reported for Plasmodium (Briggs et al, 2004;Sinden et al, 1976) and Drosophila (Han et al, 2003;Sarpal et al, 2003). These multiple situations further highlight the need to use different model organisms to study the breath of diversity in cilia and flagella .…”

Section: Discussion Ift Is Not Required For the Maintenance Of Flagelmentioning

confidence: 97%

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Fort

Bonnefoy

Kohl

et al. 2016

Journal of Cell Science

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Intraflagellar transport (IFT) is required for construction of most cilia and flagella. Here, we used electron microscopy, immunofluorescence and live video microscopy to show that IFT is absent or arrested in the mature flagellum of Trypanosoma brucei upon RNA interference (RNAi)-mediated knockdown of IFT88 and IFT140, respectively. Flagella assembled prior to RNAi did not shorten, showing that IFT is not essential for the maintenance of flagella length. Although the ultrastructure of the axoneme was not visibly affected, flagellar beating was strongly reduced and the distribution of several flagellar components was drastically modified. The R subunit of the protein kinase A was no longer concentrated in the flagellum but was largely found in the cell body whereas the kinesin 9B motor was accumulating at the distal tip of the flagellum. In contrast, the distal tip protein FLAM8 was dispersed along the flagellum. This reveals that IFT also functions in maintaining the distribution of some flagellar proteins after construction of the organelle is completed.

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“…1d). We found a much reduced proportion of homologues shared with Plasmodium, Caenorhabditis and Drosophila, which build motile or sensory cilia that are divergent in aspects of axoneme or basal body structure or formation 5 . We found that 208 TbFP proteins (Fig.…”

mentioning

confidence: 83%

Flagellar motility is required for the viability of the bloodstream trypanosome

Broadhead

Dawe

Farr

et al. 2006

Nature

Self Cite

454

607

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The 912 microtubule axoneme of flagella and cilia represents one of the most iconic structures built by eukaryotic cells and organisms. Both unity and diversity are present among cilia and flagella on the evolutionary as well as the developmental scale. Some cilia are motile, whereas others function as sensory organelles and can variously possess 912 and 910 axonemes and other associated structures 1 . How such unity and diversity are reflected in molecular repertoires is unclear. The flagellated protozoan parasite Trypanosoma brucei is endemic in sub-Saharan Africa, causing devastating disease in humans and other animals 2 . There is little hope of a vaccine for African sleeping sickness and a desperate need for modern drug therapies 3 . Here we present a detailed proteomic analysis of the trypanosome flagellum. RNA interference (RNAi)-based interrogation of this proteome provides functional insights into human ciliary diseases and establishes that flagellar function is essential to the bloodstream-form trypanosome. We show that RNAi-mediated ablation of various proteins identified in the trypanosome flagellar proteome leads to a rapid and marked failure of cytokinesis in bloodstream-form (but not procyclic insect-form) trypanosomes, suggesting that impairment of flagellar function may provide a method of disease control. A postgenomic meta-analysis, comparing the evolutionarily ancient trypanosome with other eukaryotes including humans, identifies numerous trypanosome-specific flagellar proteins, suggesting new avenues for selective intervention.Flagellum-mediated migration between the gut and salivary glands of its tsetse fly vector is essential for progression of the trypanosome life cycle. However, the necessity for motility in an extracellular bloodstream-form trypanosome is unclear. In both forms, a single attached flagellum emerges from a posterior flagellar pocket ( Fig. 1a) and comprises a membrane-bound axoneme and associated paraflagellar rod (PFR; Fig 1b). We isolated the structural axoneme and associated PFR and basal body from procyclic trypanosomes by a well-characterized procedure of detergent and high-salt treatment 4 . Bands and spots were cut from one- (Fig. 1c) and twodimensional gels and digested with trypsin, and the resulting peptides analysed by reverse-phase high-performance liquid chromatography coupled with tandem mass spectrometry. Bands and spots excised from ten representative gels were analysed, resulting in the identification of 522 nonredundant proteins.Further manual mass spectrometric validation confirmed 380 proteins (see Supplementary Methods and Supplementary Fig. 1 for peptide numbers and coverage). Highly basic proteins are known to contaminate microtubule preparations owing to charge interactions 4 , and we noted some highly basic ribosomal proteins as recognizable contaminants. To limit contamination, we filtered the data by using an isolectric point (pI) value of 10.2 as a cut-off (the pI of the most acidic ribosomal protein), and placed 49 proteins (30 of which were r...

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More than one way to build a flagellum: comparative genomics of parasitic protozoa

Cited by 115 publications

References 12 publications

Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Factors mediating plastid dependency and the origins of parasitism in apicomplexans and their close relatives

Intraflagellar transport is required for the maintenance of the trypanosome flagellum composition but not its length

Flagellar motility is required for the viability of the bloodstream trypanosome

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