Draft Genome of the Filarial Nematode Parasite \u3ci\u3eBrugia malayi\u3c/i\u3e

Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design

Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa

Babesia bovis is an apicomplexan tick-transmitted pathogen of cattle imposing a global risk and severe constraints to livestock health and economic development. The complete genome sequence was undertaken to facilitate vaccine antigen discovery, and to allow for comparative analysis with the related apicomplexan hemoprotozoa Theileria parva and Plasmodium falciparum. At 8.2 Mbp, the B. bovis genome is similar in size to that of Theileria spp. Structural features of the B. bovis and T. parva genomes are remarkably similar, and extensive synteny is present despite several chromosomal rearrangements. In contrast, B. bovis and P. falciparum, which have similar clinical and pathological features, have major differences in genome size, chromosome number, and gene complement. Chromosomal synteny with P. falciparum is limited to microregions. The B. bovis genome sequence has allowed wide scale analyses of the polymorphic variant erythrocyte surface antigen protein (ves1 gene) family that, similar to the P. falciparum var genes, is postulated to play a role in cytoadhesion, sequestration, and immune evasion. The approximately 150 ves1 genes are found in clusters that are distributed throughout each chromosome, with an increased concentration adjacent to a physical gap on chromosome 1 that contains multiple ves1-like sequences. ves1 clusters are frequently linked to a novel family of variant genes termed smorfs that may themselves contribute to immune evasion, may play a role in variant erythrocyte surface antigen protein biology, or both. Initial expression analysis of ves1 and smorf genes indicates coincident transcription of multiple variants. B. bovis displays a limited metabolic potential, with numerous missing pathways, including two pathways previously described for the P. falciparum apicoplast. This reduced metabolic potential is reflected in the B. bovis apicoplast, which appears to have fewer nuclear genes targeted to it than other apicoplast containing organisms. Finally, comparative analyses have identified several novel vaccine candidates including a positional homolog of p67 and SPAG-1, Theileria sporozoite antigens targeted for vaccine development. The genome sequence provides a greater understanding of B. bovis metabolism and potential avenues for drug therapies and vaccine development

The sequence and analysis of Trypanosoma brucei chromosome II

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational ‘hot’ and ‘cold’ regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events

The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease

Fil: El-Sayed, Najib M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Myler, Peter J. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bartholomeu, Daniella C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Nilsson, Daniel. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Aggarwal, Gautam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tran, Anh-Nhi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Ghedin, Elodie. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Worthey, Elizabeth A. Seattle Biomedical Research Institute; Estados Unidos.Fil: Delcher, Arthur L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Blandin, Gaëlle. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Westenberger, Scott J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Caler, Elisabet. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Cerqueira, Gustavo C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Haas, Carole Branched Brian. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Anupama, Atashi. Seattle Biomedical Research Institute; Estados Unidos.Fil: Arner, Erik. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Åslund, Lena. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Attipoe, Philip. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bontempi, Esteban. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Bringaud, Frédéric. Université Victor Segalen Bordeaux II. Laboratoire de Génomique Fonctionnelle des Trypanosomatides; Francia.Fil: Burton, Peter. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Cadag, Eithon. Seattle Biomedical Research Institute; Estados Unidos.Fil: Campbell, David A. University of California. Department of Microbiology; Estados Unidos.Fil: Carrington, Mark. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Crabtree, Jonathan. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Darban, Hamid. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Silveira, Jose Franco da. Universidade Federal de Sao Paulo. Departamento de Microbiologia; Brasil.Fil: Jong, Pieter de. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Edwards, Kimberly. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Englund, Paul T. Johns Hopkins University School of Medicine. Department of Biological Chemistry; Estados Unidos.Fil: Fazelina, Gholam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Feldblyum, Tamara. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ferella, Marcela. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Frasch, Alberto Carlos. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Gull, Keith. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Horn, David. London School of Hygiene and Tropical Medicine; Reino Unido.Fil: Hou, Lihua. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Huang, Yiting. Seattle Biomedical Research Institute; Estados Unidos.Fil: Kindlund, Ellen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Klingbeil, Michele. University of Massachusetts. Department of Microbiology; Estados Unidos.Fil: Kluge, Sindy. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Koo, Hean. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Lacerda, Daniela. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Levin, Mariano J. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Lorenzi, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Louie, Tin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Machado, Carlos Renato. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: McCulloch, Richard. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: McKenna, Alan. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mizuno, Yumi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mottram, Jeremy C. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Nelson, Siri. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ochaya, Stephen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Osoegawa, Kazutoyo. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Pai, Grace. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Parsons, Marilyn. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pentony, Martin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pettersson, Ulf. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Pop, Mihai. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ramirez, Jose Luis. Universidad Central de Venezuela. Instituto de Biología Experimental; Venezuela.Fil: Rinta, Joel. Seattle Biomedical Research Institute; Estados Unidos.Fil: Robertson, Laura. Seattle Biomedical Research Institute; Estados Unidos.Fil: Salzberg, Steven L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sanchez, Daniel O. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Seyler, Amber. Seattle Biomedical Research Institute; Estados Unidos.Fil: Sharma, Reuben. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Shetty, Jyoti. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Simpson, Anjana J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sisk, Ellen. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tammi, Martti T. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Tarleton, Rick. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos.Fil: Teixeira, Santuza. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: Aken, Susan Van. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Vogt, Christy. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ward, Pauline N. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Wickstead, Bill. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Wortman, Jennifer. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: White, Owen. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Fraser, Claire M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Stuart, Kenneth D. Seattle Biomedical Research Institute; Estados Unidos.Fil: Andersson, Björn. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention

The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease

Fil: El-Sayed, Najib M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Myler, Peter J. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bartholomeu, Daniella C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Nilsson, Daniel. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Aggarwal, Gautam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tran, Anh-Nhi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Ghedin, Elodie. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Worthey, Elizabeth A. Seattle Biomedical Research Institute; Estados Unidos.Fil: Delcher, Arthur L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Blandin, Gaëlle. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Westenberger, Scott J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Caler, Elisabet. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Cerqueira, Gustavo C. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Haas, Carole Branched Brian. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Anupama, Atashi. Seattle Biomedical Research Institute; Estados Unidos.Fil: Arner, Erik. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Åslund, Lena. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Attipoe, Philip. Seattle Biomedical Research Institute; Estados Unidos.Fil: Bontempi, Esteban. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Bringaud, Frédéric. Université Victor Segalen Bordeaux II. Laboratoire de Génomique Fonctionnelle des Trypanosomatides; Francia.Fil: Burton, Peter. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Cadag, Eithon. Seattle Biomedical Research Institute; Estados Unidos.Fil: Campbell, David A. University of California. Department of Microbiology; Estados Unidos.Fil: Carrington, Mark. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Crabtree, Jonathan. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Darban, Hamid. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Silveira, Jose Franco da. Universidade Federal de Sao Paulo. Departamento de Microbiologia; Brasil.Fil: Jong, Pieter de. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Edwards, Kimberly. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Englund, Paul T. Johns Hopkins University School of Medicine. Department of Biological Chemistry; Estados Unidos.Fil: Fazelina, Gholam. Seattle Biomedical Research Institute; Estados Unidos.Fil: Feldblyum, Tamara. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ferella, Marcela. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Frasch, Alberto Carlos. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Gull, Keith. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Horn, David. London School of Hygiene and Tropical Medicine; Reino Unido.Fil: Hou, Lihua. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Huang, Yiting. Seattle Biomedical Research Institute; Estados Unidos.Fil: Kindlund, Ellen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Klingbeil, Michele. University of Massachusetts. Department of Microbiology; Estados Unidos.Fil: Kluge, Sindy. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Koo, Hean. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Lacerda, Daniela. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Levin, Mariano J. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Lorenzi, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-CYTED project). Laboratorio de Biología Molecular de la Enfermedad de Chagas; Argentina.Fil: Louie, Tin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Machado, Carlos Renato. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: McCulloch, Richard. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: McKenna, Alan. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mizuno, Yumi. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Mottram, Jeremy C. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Nelson, Siri. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ochaya, Stephen. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Osoegawa, Kazutoyo. Children’s Hospital Oakland Research Institute. BACPAC Resources; Estados Unidos.Fil: Pai, Grace. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Parsons, Marilyn. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pentony, Martin. Seattle Biomedical Research Institute; Estados Unidos.Fil: Pettersson, Ulf. Uppsala University. Department of Genetics and Pathology; Suecia.Fil: Pop, Mihai. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Ramirez, Jose Luis. Universidad Central de Venezuela. Instituto de Biología Experimental; Venezuela.Fil: Rinta, Joel. Seattle Biomedical Research Institute; Estados Unidos.Fil: Robertson, Laura. Seattle Biomedical Research Institute; Estados Unidos.Fil: Salzberg, Steven L. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sanchez, Daniel O. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina.Fil: Seyler, Amber. Seattle Biomedical Research Institute; Estados Unidos.Fil: Sharma, Reuben. University of Cambridge. Department of Biochemistry; Reino Unido.Fil: Shetty, Jyoti. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Simpson, Anjana J. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Sisk, Ellen. Seattle Biomedical Research Institute; Estados Unidos.Fil: Tammi, Martti T. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Fil: Tarleton, Rick. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos.Fil: Teixeira, Santuza. Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia; Brasil.Fil: Aken, Susan Van. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Vogt, Christy. Seattle Biomedical Research Institute; Estados Unidos.Fil: Ward, Pauline N. University of Glasgow. Wellcome Centre for Molecular Parasitology; Reino Unido.Fil: Wickstead, Bill. University of Oxford. Sir William Dunn School of Pathology; Reino Unido.Fil: Wortman, Jennifer. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: White, Owen. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Fraser, Claire M. The Institute for Genomic Research. Department of Parasite Genomics; Estados Unidos.Fil: Stuart, Kenneth D. Seattle Biomedical Research Institute; Estados Unidos.Fil: Andersson, Björn. Karolinska Institutet. Center for Genomics and Bioinformatics; Suecia.Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention

Genome sequence of Aedes aegypti, a major arbovirus vector

We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species

The genome of the African trypanosome Trypanosoma brucei

African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of <i>Trypanosoma brucei</i>. The 26-megabase genome contains 9068 predicted genes, including ~900 pseudogenes and ~1700 <i>T. brucei</i>–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of <i>T. brucei</i>, <i>T. cruzi</i>, and <i>Leishmania major</i> reveals the least overall metabolic capability in <i>T. brucei</i> and the greatest in <i>L. major</i>. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified