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

ABSTRACT

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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    • "This verifies the requirement of TfR to scavenge iron for the BS trypanosomes in mammalian blood. Unexpectedly, a comparative phylogenetic analysis of the surface proteins of trypanosomatids revealed that the basal-branching Trypanosoma vivax lacks the TfR gene, which is compatible with a rather late development of the gene following the emergence of the T. congolense and T. brucei clade [24]. Apart from transferrin, trypanosomes can take advantage of the iron-rich lactoferrin of the host, which is an iron-binding glycoprotein belonging to the transferrin family [25]. "
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    ABSTRACT: Background Every eukaryote requires iron, which is also true for the parasitic protist Trypanosoma brucei, the causative agent of sleeping sickness in humans and cattle in Africa. T. brucei undergoes a complex life cycle during which its single mitochondrion is subject to major metabolic and morphological changes. Scope of Review This review covers what is known about processes associated with iron-sulfur clusters and heme metabolism in T. brucei. We discuss strategies by which iron and heme are acquired and utilized by this model parasite, emphasizing the differences between its two life cycle stages residing in the bloodstream of the mammalian host and gut of the insect vector. Finally, the role of iron in the host-parasite interactions is discussed along with their possible exploitation in fighting these deadly parasites. Major Conclusions The processes associated with acquisition and utilization of iron, distinct in the two life stages of T. brucei, are fine tuned for the dramatically different host environment occupied by them. Although the composition and compartmentalization of the iron-sulfur cluster assembly seem to be conserved, some unique features of the iron acquisition strategies may be exploited for medical interventions against these parasites. General Significance As early-branching protists, trypanosomes and related flagellates are known to harbor an array of unique features, with the acquisition of iron being another peculiarity. Thanks to intense research within the last decade, understanding of iron-sulfur cluster assembly and iron metabolism in T. brucei is among the most advanced of all eukaryotes.
    Full-text · Article · Oct 2015 · Biochimica et Biophysica Acta (BBA) - General Subjects
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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.
    Full-text · Article · Sep 2015 · Molecular and Biochemical Parasitology
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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.
    Full-text · Article · May 2014 · Nucleic Acids Research
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