The African parasites Tr. brucei gambiense and Tr. b. rhodesiense cause human sleeping sickness, whereas Tr. b. brucei infects cattle in subsaharan Africa, causing the Nagana disease. The South American parasite Tr. cruzi, on the other hand, is the causative agent of human Chagas disease. Tr. brucei posses a nuclear genome as well as a 35-Mbp kinetoplast genome. The nuclear genome is split into three classes of chromosomes and contains 11 megabase chromosomes (0.9-5.7 Mbp),

19.6 The Pathogenic Diplomanad Giardia and the Parabasalid Trichomonas | 431

intermediate chromosomes (300-900kbp), and minichromosomes (50-100kbp). Chromosome 1 was recently published [89], and genome sequencing of Tr. brucei and Tr.cruzi species is ongoing (Table 19.1). Genome sequencing has helped our understanding of the genomic organization of the variant surface antigen genes (VSG; Fig. 19.2), which encode the coat proteins that uniformly cover the surface of the Tr. brucei bloodstage parasite. Tr. brucei evades the host immune system by stochastic switching of surface antigen expression in a fraction of the parasite population. The active VSG gene is transcribed in one of approximately 20 telomeric expression sites, whose structures were recently characterized via sequencing [90].

19.5.2 Leishmania

Leishmania parasites are transmitted to humans by the bite of a sandfly and cause visceral, cutaneous, or mucosal lesions. An estimated two million people are infected per year in tropical and temperate regions of the word. Sequencing of the Old World pathogen L. major began in 1994, and the complete sequences of 2 out of 36 chromosomes have been published [91-92]. The Leishmania genome sequencing project recently confirmed the remarkable observation of large poly-cistronic transcribed units (reviewed in Ref. [93]) composed of blocks of genes encoded on the same DNA strand [91, 92, 94]. All identified genes in the completed chromosomes 1-3 are oriented within such polycistronic clusters, with the creation of discrete mRNAs created by trans-splicing [95]. Leishmania genes, thought to be largely free of introns, constitute a 34-Mbp high-density genome, 45% of which are estimated to be protein coding regions. The recent shotgun sequencing of the Latin American pathogen L. braziliensis obtained 15% of the parasite haploid genome. BLAST search revealed 45.3-60.2% similarity to L. major [96].

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