Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas Disease
Najib M. El-Sayed,1,2*Peter J. Myler,3,4,5*Daniella C. Bartholomeu,1Daniel Nilsson,6Gautam Aggarwal,3Anh-Nhi Tran,6Elodie Ghedin,1,2Elizabeth A. Worthey,3Arthur L. Delcher,1Gaëlle Blandin,1Scott J. Westenberger,1,7Elisabet Caler,1Gustavo C. Cerqueira,1,8Carole Branche,6Brian Haas,1Atashi Anupama,3Erik Arner,6Lena Åslund,9Philip Attipoe,3Esteban Bontempi,6,10Frédéric Bringaud,11Peter Burton,12Eithon Cadag,3David A. Campbell,7Mark Carrington,13Jonathan Crabtree,1Hamid Darban,6Jose Franco da Silveira,14Pieter de Jong,15Kimberly Edwards,6Paul T. Englund,16Gholam Fazelina,3Tamara Feldblyum,1Marcela Ferella,6Alberto Carlos Frasch,17Keith Gull,18David Horn,19Lihua Hou,1Yiting Huang,3Ellen Kindlund,6Michele Klingbeil,20Sindy Kluge,6Hean Koo,1Daniela Lacerda,1,21Mariano J. Levin,22Hernan Lorenzi,22Tin Louie,3Carlos Renato Machado,8Richard McCulloch,12Alan McKenna,6Yumi Mizuno,6Jeremy C. Mottram,12Siri Nelson,3Stephen Ochaya,6Kazutoyo Osoegawa,15Grace Pai,1Marilyn Parsons,3,4Martin Pentony,3Ulf Pettersson,9Mihai Pop,1Jose Luis Ramirez,23Joel Rinta,3Laura Robertson,3Steven L. Salzberg,1Daniel O. Sanchez,17Amber Seyler,3Reuben Sharma,13Jyoti Shetty,1Anjana J. Simpson,1Ellen Sisk,3Martti T. Tammi,6,24Rick Tarleton,25Santuza Teixeira,8Susan Van Aken,1Christy Vogt,3Pauline N. Ward,12Bill Wickstead,18Jennifer Wortman,1Owen White,1Claire M. Fraser,1Kenneth D. Stuart,3,4Björn Andersson6
Whole-genome sequencing of the protozoan pathogen Trypanosomacruzi revealed that the diploid genome contains a predicted22,570 proteins encoded by genes, of which 12,570 representallelic pairs. Over 50% of the genome consists of repeated sequences,such as retrotransposons and genes for large families of surfacemolecules, which include trans-sialidases, mucins, gp63s, anda large novel family (>1300 copies) of mucin-associated surfaceprotein (MASP) genes. Analyses of the T. cruzi, T. brucei, andLeishmania major (Tritryp) genomes imply differences from othereukaryotes in DNA repair and initiation of replication and reflecttheir unusual mitochondrial DNA. Although the Tritryp lack severalclasses of signaling molecules, their kinomes contain a largeand diverse set of protein kinases and phosphatases; their sizeand diversity imply previously unknown interactions and regulatoryprocesses, which may be targets for intervention.
1 Department of Parasite Genomics, The Institute for Genomic Research, Rockville, MD 20850, USA. 2 Department of Microbiology and Tropical Medicine, George Washington University, Washington, DC 20052, USA. 3 Seattle Biomedical Research Institute, Seattle, WA 98109, USA. 4 Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA. 5 Department of Medical Education and Biomedical Informatics, University of Washington, Seattle, WA 98195, USA. 6 Center for Genomics and Bioinformatics, Karolinska Institutet, Berzelius väg 35, S-171 77 Stockholm, Sweden. 7 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA. 8 Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil. 9 Department of Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden. 10 Instituto Nacional de Parasitología Dr. M. Fatala Chabén, Administración Nacional de Laboratories e Insitutos de Salud (ANLIS), 1063, Buenos Aires, Argentina. 11 Laboratoire de Génomique Fonctionnelle des Trypanosomatides, UMR-CNRS 5162, Université Victor Segalen Bordeaux II, 33076 Bordeaux Cedex, France. 12 Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow G11 6NU, Scotland, UK. 13 Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. 14 Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, CEP 04023–062, São Paulo, SP, Brazil. 15 BACPAC Resources, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. 16 Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 17 Instituto de Investigaciones Biotecnológicas–Instituto Tecnológico de Chascómús, National University of San Martin and National Research Council, 1650 Buenos Aires, Argentina. 18 Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. 19 London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. 20 Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA. 21 René Rachou Research Center/CPqRR, Oswaldo Cruz Foundation, Belo Horizonte, MG, Brazil. 22 Laboratory of Molecular Biology of Chagas Disease, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, National Research Council (CONICET-CYTED project), School of Sciences, Centro de Genomica Aplicada-CeGA-University of Buenos Aires, 1428 Buenos Aires, Argentina. 23 Instituto de Biología Experimental, Universidad Central de Venezuela and ADEA-MCT, 1041-A Caracas, Venezuela. 24 Departments of Biological Sciences and Biochemistry, National University of Singapore, Singapore. 25 Center for Tropical and Emerging Global Diseases, Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: nelsayed{at}tigr.org (N.M.E.-S.); peter.myler{at}sbri.org (P.J.M.); bjorn.andersson{at}cgb.ki.se (B.A.)
The editors suggest the following Related Resources on Science sites:
In Science Magazine
INTRODUCTION TO SPECIAL ISSUE
Caroline Ash and Barbara R. Jasny (15 July 2005) Science309 (5733), 399.
[DOI: 10.1126/science.309.5733.399] |Summary »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
TriTrypDB: a functional genomic resource for the Trypanosomatidae.
M. Aslett, C. Aurrecoechea, M. Berriman, J. Brestelli, B. P. Brunk, M. Carrington, D. P. Depledge, S. Fischer, B. Gajria, X. Gao, et al. (2009)
Nucleic Acids Res.
|Abstract »|Full Text »|PDF »
Trypanosomatid Genomes Contain Several Subfamilies of ingi-Related Retroposons.
F. Bringaud, M. Berriman, and C. Hertz-Fowler (2009)
Eukaryot. Cell
8, 1532-1542
|Abstract »|Full Text »|PDF »
Trypanosome Prereplication Machinery Contains a Single Functional Orc1/Cdc6 Protein, Which Is Typical of Archaea.
P. D. d. M. Godoy, L. A. Nogueira-Junior, L. S. Paes, A. Cornejo, R. M. Martins, A. M. Silber, S. Schenkman, and M. C. Elias (2009)
Eukaryot. Cell
8, 1592-1603
|Abstract »|Full Text »|PDF »
Molecular analysis of a UDP-GlcNAc:polypeptide {alpha}-N-acetylglucosaminyltransferase implicated in the initiation of mucin-type O-glycosylation in Trypanosoma cruzi.
N. Heise, D. Singh, H. van der Wel, S. O Sassi, J. M Johnson, C. L Feasley, C. M Koeller, J. O Previato, L. Mendonca-Previato, and C. M West (2009)
Glycobiology
19, 918-933
|Abstract »|Full Text »|PDF »
Insufficient TLR Activation Contributes to the Slow Development of CD8+ T Cell Responses in Trypanosoma cruzi Infection.
A. M. Padilla, L. J. Simpson, and R. L. Tarleton (2009)
J. Immunol.
183, 1245-1252
|Abstract »|Full Text »|PDF »
Prizes and Parasites: Incentive Models for Addressing Chagas Disease.
S. E. Crager and M. Price (2009)
J. Law Med. Ethics
37, 292-304
|PDF »
Comparison of Recombinant Trypanosoma cruzi Peptide Mixtures versus Multiepitope Chimeric Proteins as Sensitizing Antigens for Immunodiagnosis.
C. Camussone, V. Gonzalez, M. S. Belluzo, N. Pujato, M. E. Ribone, C. M. Lagier, and I. S. Marcipar (2009)
Clin. Vaccine Immunol.
16, 899-905
|Abstract »|Full Text »|PDF »
Probing Population Dynamics of Trypanosoma cruzi during Progression of the Chronic Phase in Chagasic Patients.
D. A. D'Avila, A. M. Macedo, H. M. S. Valadares, E. D. Gontijo, A. M. de Castro, C. R. Machado, E. Chiari, and L. M. C. Galvao (2009)
J. Clin. Microbiol.
47, 1718-1725
|Abstract »|Full Text »|PDF »
Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi.
D. C. Bartholomeu, G. C. Cerqueira, A. C. A. Leao, W. D. daRocha, F. S. Pais, C. Macedo, A. Djikeng, S. M. R. Teixeira, and N. M. El-Sayed (2009)
Nucleic Acids Res.
37, 3407-3417
|Abstract »|Full Text »|PDF »
Novel Mitochondrial Complex II Isolated from Trypanosoma cruzi Is Composed of 12 Peptides Including a Heterodimeric Ip Subunit.
J. Morales, T. Mogi, S. Mineki, E. Takashima, R. Mineki, H. Hirawake, K. Sakamoto, S. Omura, and K. Kita (2009)
J. Biol. Chem.
284, 7255-7263
|Abstract »|Full Text »|PDF »
Combining RNA Interference Mutants and Comparative Proteomics to Identify Protein Components and Dependences in a Eukaryotic Flagellum.
N. Portman, S. Lacomble, B. Thomas, P. G. McKean, and K. Gull (2009)
J. Biol. Chem.
284, 5610-5619
|Abstract »|Full Text »|PDF »
TcSNP: a database of genetic variation in Trypanosoma cruzi.
A. A. Ackermann, S. J. Carmona, and F. Aguero (2009)
Nucleic Acids Res.
37, D544-D549
|Abstract »|Full Text »|PDF »
Immunological Dominance of Trypanosoma cruzi Tandem Repeat Proteins.
Novel Protective Antigens Expressed by Trypanosoma cruzi Amastigotes Provide Immunity to Mice Highly Susceptible to Chagas' Disease.
E. L. V. Silveira, C. Claser, F. A. B. Haolla, L. G. Zanella, and M. M. Rodrigues (2008)
Clin. Vaccine Immunol.
15, 1292-1300
|Abstract »|Full Text »|PDF »
Recruitment and Endo-Lysosomal Activation of TLR9 in Dendritic Cells Infected with Trypanosoma cruzi.
D. C. Bartholomeu, C. Ropert, M. B. Melo, P. Parroche, C. F. Junqueira, S. M. R. Teixeira, C. Sirois, P. Kasperkovitz, C. F. Knetter, E. Lien, et al. (2008)
J. Immunol.
181, 1333-1344
|Abstract »|Full Text »|PDF »
Glucose-induced Remodeling of Intermediary and Energy Metabolism in Procyclic Trypanosoma brucei.
V. Coustou, M. Biran, M. Breton, F. Guegan, L. Riviere, N. Plazolles, D. Nolan, M. P. Barrett, J.-M. Franconi, and F. Bringaud (2008)
J. Biol. Chem.
283, 16342-16354
|Abstract »|Full Text »|PDF »
Histone Acetylation and Methylation at Sites Initiating Divergent Polycistronic Transcription in Trypanosoma cruzi.
P. Respuela, M. Ferella, A. Rada-Iglesias, and L. Aslund (2008)
J. Biol. Chem.
283, 15884-15892
|Abstract »|Full Text »|PDF »
Autophagy Is Involved in Nutritional Stress Response and Differentiation in Trypanosoma cruzi.
V. E. Alvarez, G. Kosec, C. Sant'Anna, V. Turk, J. J. Cazzulo, and B. Turk (2008)
J. Biol. Chem.
283, 3454-3464
|Abstract »|Full Text »|PDF »
Sequence Diversity of the Trypanosoma cruzi Complement Regulatory Protein Family.
Neglected tropical cardiomyopathies: I. Chagas disease.
S. Yacoub, A. O. Mocumbi, and M. H Yacoub (2008)
Heart
94, 244-248
|Full Text »|PDF »
Infection with Trypanosoma cruzi Restricts the Repertoire of Parasite-Specific CD8+ T Cells Leading to Immunodominance.
F. Tzelepis, B. C. G. de Alencar, M. L. O. Penido, C. Claser, A. V. Machado, O. Bruna-Romero, R. T. Gazzinelli, and M. M. Rodrigues (2008)
J. Immunol.
180, 1737-1748
|Abstract »|Full Text »|PDF »
ProtozoaDB: dynamic visualization and exploration of protozoan genomes.
A. M. R. Davila, P. N. Mendes, G. Wagner, D. A. Tschoeke, R. R. C. Cuadrat, F. Liberman, L. Matos, T. Satake, K. A. C. S. Ocana, O. Triana, et al. (2008)
Nucleic Acids Res.
36, D547-D552
|Abstract »|Full Text »|PDF »
Trans-Sialidase Recombinant Protein Mixed with CpG Motif-Containing Oligodeoxynucleotide Induces Protective Mucosal and Systemic Trypanosoma cruzi Immunity Involving CD8+ CTL and B Cell-Mediated Cross-Priming.
D. F. Hoft, C. S. Eickhoff, O. K. Giddings, J. R. C. Vasconcelos, and M. M. Rodrigues (2007)
J. Immunol.
179, 6889-6900
|Abstract »|Full Text »|PDF »
Overexpression of a Zn2+-sensitive Soluble Exopolyphosphatase from Trypanosoma cruzi Depletes Polyphosphate and Affects Osmoregulation.
J. Fang, F. A. Ruiz, M. Docampo, S. Luo, J. C. F. Rodrigues, L. S. Motta, P. Rohloff, and R. Docampo (2007)
J. Biol. Chem.
282, 32501-32510
|Abstract »|Full Text »|PDF »
Novel Membrane-Bound eIF2{alpha} Kinase in the Flagellar Pocket of Trypanosoma brucei.
M. C. S. Moraes, T. C. L. Jesus, N. N. Hashimoto, M. Dey, K. J. Schwartz, V. S. Alves, C. C. Avila, J. D. Bangs, T. E. Dever, S. Schenkman, et al. (2007)
Eukaryot. Cell
6, 1979-1991
|Abstract »|Full Text »|PDF »
Ohno's dilemma: Evolution of new genes under continuous selection.
U. Bergthorsson, D. I. Andersson, and J. R. Roth (2007)
PNAS
104, 17004-17009
|Abstract »|Full Text »|PDF »
Telomeric co-localization of the modified base J and contingency genes in the protozoan parasite Trypanosoma cruzi.
D. K. Ekanayake, M. J. Cipriano, and R. Sabatini (2007)
Nucleic Acids Res.
35, 6367-6377
|Abstract »|Full Text »|PDF »
Internal and Surface-Localized Major Surface Proteases of Leishmania spp. and Their Differential Release from Promastigotes.
C. Yao, J. E. Donelson, and M. E. Wilson (2007)
Eukaryot. Cell
6, 1905-1912
|Abstract »|Full Text »|PDF »
Cyclic Nucleotide Signaling Mechanisms in Trypanosomes: Possible Targets for Therapeutic Agents.
New Trypanosoma cruzi Repeated Element That Shows Site Specificity for Insertion.
R. T. Souza, M. R. M. Santos, F. M. Lima, N. M. El-Sayed, P. J. Myler, J. C. Ruiz, and J. F. da Silveira (2007)
Eukaryot. Cell
6, 1228-1238
|Abstract »|Full Text »|PDF »
Trypanosoma brucei homologous recombination is dependent on substrate length and homology, though displays a differential dependence on mismatch repair as substrate length decreases.
The L1Tc non-LTR retrotransposon of Trypanosoma cruzi contains an internal RNA-pol II-dependent promoter that strongly activates gene transcription and generates unspliced transcripts.
S. R. Heras, M. C. Lopez, M. Olivares, and M. C. Thomas (2007)
Nucleic Acids Res.
35, 2199-2214
|Abstract »|Full Text »|PDF »
Molecular and Functional Analyses of a Novel Class I Secretory Nuclease from the Human Pathogen, Leishmania donovani.
Genome-Wide Analysis of C/D and H/ACA-Like Small Nucleolar RNAs in Leishmania major Indicates Conservation among Trypanosomatids in the Repertoire and in Their rRNA Targets.
X.-h. Liang, A. Hury, E. Hoze, S. Uliel, I. Myslyuk, A. Apatoff, R. Unger, and S. Michaeli (2007)
Eukaryot. Cell
6, 361-377
|Abstract »|Full Text »|PDF »
Deletion of a trypanosome telomere leads to loss of silencing and progressive loss of terminal DNA in the absence of cell cycle arrest.
L. Glover, S. Alsford, C. Beattie, and D. Horn (2007)
Nucleic Acids Res.
35, 872-880
|Abstract »|Full Text »|PDF »
Roles of a Trypanosoma brucei 5'->3' exoribonuclease homolog in mRNA degradation.
C.-H. Li, H. Irmer, D. Gudjonsdottir-Planck, S. Freese, H. Salm, S. Haile, A. M. Estevez, and C. Clayton (2006)
RNA
12, 2171-2186
|Abstract »|Full Text »|PDF »
Modulation of Leishmania ABC Protein Gene Expression through Life Stages and among Drug-Resistant Parasites..
P. Leprohon, D. Legare, I. Girard, B. Papadopoulou, and M. Ouellette (2006)
Eukaryot. Cell
5, 1713-1725
|Abstract »|Full Text »|PDF »
Fumarate Is an Essential Intermediary Metabolite Produced by the Procyclic Trypanosoma brucei.
V. Coustou, M. Biran, S. Besteiro, L. Riviere, T. Baltz, J.-M. Franconi, and F. Bringaud (2006)
J. Biol. Chem.
281, 26832-26846
|Abstract »|Full Text »|PDF »
Chromosome-wide analysis of gene function by RNA interference in the african trypanosome..
C. Subramaniam, P. Veazey, S. Redmond, J. Hayes-Sinclair, E. Chambers, M. Carrington, K. Gull, K. Matthews, D. Horn, and M. C. Field (2006)
Eukaryot. Cell
5, 1539-1549
|Abstract »|Full Text »|PDF »
Chagas' Disease -- Can We Stop the Deaths?.
J. H. Maguire (2006)
N. Engl. J. Med.
355, 760-761
|Full Text »|PDF »
Molecular Cloning of a Trypanosoma cruzi Cell Surface Casein Kinase II Substrate, Tc-1, Involved in Cellular Infection.
S. A. J. Augustine, Y. Y. Kleshchenko, P. N. Nde, S. Pratap, E. A. Ager, J. M. Burns Jr, M. F. Lima, and F. Villalta (2006)
Infect. Immun.
74, 3922-3929
|Abstract »|Full Text »|PDF »
A TFIIB-like protein is indispensable for spliced leader RNA gene transcription in Trypanosoma brucei.
B. Schimanski, J. Brandenburg, T. N. Nguyen, M. J. Caimano, and A. Gunzl (2006)
Nucleic Acids Res.
34, 1676-1684
|Abstract »|Full Text »|PDF »
From the Cover: New insights into myosin evolution and classification.
Molecular Characterization of Serine-, Alanine-, and Proline-Rich Proteins of Trypanosoma cruzi and Their Possible Role in Host Cell Infection.
R. C. P. Baida, M. R. M. Santos, M. S. Carmo, N. Yoshida, D. Ferreira, A. T. Ferreira, N. M. El Sayed, B. Andersson, and J. F. da Silveira (2006)
Infect. Immun.
74, 1537-1546
|Abstract »|Full Text »|PDF »
CYP51 from Trypanosoma cruzi: A PHYLA-SPECIFIC RESIDUE IN THE B' HELIX DEFINES SUBSTRATE PREFERENCES OF STEROL 14{alpha}-DEMETHYLASE.
G. I. Lepesheva, N. G. Zaitseva, W. D. Nes, W. Zhou, M. Arase, J. Liu, G. C. Hill, and M. R. Waterman (2006)
J. Biol. Chem.
281, 3577-3585
|Abstract »|Full Text »|PDF »
The Trypanosoma cruzi L1Tc and NARTc Non-LTR Retrotransposons Show Relative Site Specificity for Insertion.
F. Bringaud, D. C. Bartholomeu, G. Blandin, A. Delcher, T. Baltz, N. M. A. El-Sayed, and E. Ghedin (2006)
Mol. Biol. Evol.
23, 411-420
|Abstract »|Full Text »|PDF »
RNA-Binding Domain Proteins in Kinetoplastids: a Comparative Analysis.
J. De Gaudenzi, A. C. Frasch, and C. Clayton (2005)
Eukaryot. Cell
4, 2106-2114
|Abstract »|Full Text »|PDF »
Genome update: distribution of two-component transduction systems in 250 bacterial genomes.
K. Kiil, J. B. Ferchaud, C. David, T. T. Binnewies, H. Wu, T. Sicheritz-Ponten, H. Willenbrock, and D. W. Ussery (2005)
Microbiology
151, 3447-3452
|Full Text »|PDF »
Comparative Genomics of Trypanosomatid Parasitic Protozoa.
N. M. El-Sayed, P. J. Myler, G. Blandin, M. Berriman, J. Crabtree, G. Aggarwal, E. Caler, H. Renauld, E. A. Worthey, C. Hertz-Fowler, et al. (2005)
Science
309, 404-409
|Abstract »|Full Text »|PDF »
The Genome of the Kinetoplastid Parasite, Leishmania major.
A. C. Ivens, C. S. Peacock, E. A. Worthey, L. Murphy, G. Aggarwal, M. Berriman, E. Sisk, M.-A. Rajandream, E. Adlem, R. Aert, et al. (2005)
Science
309, 436-442
|Abstract »|Full Text »|PDF »
To whom correspondence should be addressed. E-mail: 
