A Cell-surface Phylome for African Trypanosomes

Pathogen Genomics Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England, United Kingdom
PLoS Neglected Tropical Diseases (Impact Factor: 4.45). 03/2013; 7(3):e2121. DOI: 10.1371/journal.pntd.0002121
Source: PubMed


The cell surface of Trypanosoma brucei, like many protistan blood parasites, is crucial for mediating host-parasite interactions and is instrumental to the initiation, maintenance and severity of infection. Previous comparisons with the related trypanosomatid parasites T. cruzi and Leishmania major suggest that the cell-surface proteome of T. brucei is largely taxon-specific. Here we compare genes predicted to encode cell surface proteins of T. brucei with those from two related African trypanosomes, T. congolense and T. vivax. We created a cell surface phylome (CSP) by estimating phylogenies for 79 gene families with putative surface functions to understand the more recent evolution of African trypanosome surface architecture. Our findings demonstrate that the transferrin receptor genes essential for bloodstream survival in T. brucei are conserved in T. congolense but absent from T. vivax and include an expanded gene family of insect stage-specific surface glycoproteins that includes many currently uncharacterized genes. We also identify species-specific features and innovations and confirm that these include most expression site-associated genes (ESAGs) in T. brucei, which are absent from T. congolense and T. vivax. The CSP presents the first global picture of the origins and dynamics of cell surface architecture in African trypanosomes, representing the principal differences in genomic repertoire between African trypanosome species and provides a basis from which to explore the developmental and pathological differences in surface architectures. All data can be accessed at: http://www.genedb.org/Page/trypanosoma_surface_phylome.

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    • "midgut stages; similar forms can be cultured in vitro (procyclic cultured forms, PCF). Reflecting their vastly different environments, BF and PCF differ widely in gene expression, particularly with respect to metabolism and surface antigen expression [1] [2] [3] [4] [5]. The 35 megabase haploid genome of T. b. brucei (hereafter T. brucei ) includes eleven large chromosomes that are thought to encode all active genes [6]. "
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    ABSTRACT: Since the initial publication of the trypanosomatid genomes, curation has been ongoing. Here we make use of existing Trypanosoma brucei ribosome profiling data to provide evidence of ribosome occupancy (and likely translation) of mRNAs from 225 currently unannotated coding sequences (CDSs). A small number of these putative genes correspond to extra copies of previously annotated genes, but 85% are novel. The median size of these novels CDSs is small (81 aa), indicating that past annotation work has excelled at detecting large CDSs. Of the unique CDSs confirmed here, over half have candidate orthologues in other trypanosomatid genomes, most of which were not yet annotated as protein-coding genes. Nonetheless, approximately one-third of the new CDSs were found only in T. brucei subspecies. Using ribosome footprints, RNA-Seq and spliced leader mapping data, we updated previous work to definitively revise the start sites for 414CDSs as compared to the current gene models. The data pointed to several regions of the genome that had sequence errors that altered coding region boundaries. Finally, we consolidated this data with our previous work to propose elimination of 683 putative genes as protein-coding and arrive at a view of the translatome of slender bloodstream and procyclic culture form T. brucei.
    Molecular and Biochemical Parasitology 09/2015; 202(2). DOI:10.1016/j.molbiopara.2015.09.002 · 1.79 Impact Factor
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    • "There is no orthology between the ves1 in different Babesia spp. (Figure 4), just as there are no orthologous vsg in different African trypanosome genomes (31,88), orthologous var in comparisons of P. falciparum and P. reichenowi (35), or indeed among P. falciparum strains (82). The mutual exclusivity of repertoires in these situations indicates rapid gene turnover; the frequent gain and loss of gene copies after speciation, resulting in the substitution of shared, ancestral characters by unique, derived ones. "
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    ABSTRACT: Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5′ ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.
    Nucleic Acids Research 05/2014; 42(11). DOI:10.1093/nar/gku322 · 9.11 Impact Factor
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    • "This cell surface phylome provided a detailed analysis of species-specific gene families and of gene gain and loss in shared families, aiding in the identification of surface proteins that may mediate specific aspects of pathogenesis and disease progression. In order to further discuss our results, we evaluated which proteins from the T. brucei cell surface phylome [35] were common to the list of twenty-four T. brucei immunodiagnostic antigens that were found by Sullivan et al. [34]. African trypanosome genomes contain large VSG gene families [32, 33], but monoallelic expression of a single gene is ensured because transcription is restricted to telomeric VSG expression sites (ES) [36–38]. "
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    ABSTRACT: Trypanosoma evansi and Trypanosoma vivax, which are the major causative agents of animal trypanosomosis in Venezuela, have shown a very high immunological cross-reactivity. Since the production of T. vivax antigens is a limiting factor as this parasite is difficult to propagate in experimental animal models, our goal has been to identify and isolate antigens from T. evansi that cross-react with T. vivax. Here, we used the Venezuelan T. evansi TEVA1 isolate to prepare the total parasite lysate and its corresponding cytosolic and membranous fractions. In order to extract the T. evansi integral membrane proteins, the particulate portion was further extracted first with Triton X-100, and then with sodium dodecyl sulfate. After discarding the cytosolic and Triton X-100 solubilized proteins, we employed sedimentation by centrifugation on linear sucrose gradients to partially purify the sodium dodecyl sulfate-solubilized proteins from the Triton X-100 resistant particulate fraction of T. evansi. We obtained enriched pools containing polypeptide bands with apparent molecular masses of 27 kDa, 31 kDa, and 53 kDa, which were recognized by anti-T. vivax antibodies from experimentally and naturally infected bovines.
    Journal of Parasitology Research 03/2014; 2014(2):965815. DOI:10.1155/2014/965815
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