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Science 15 July 2005:
Vol. 309. no. 5733, pp. 436 - 442
DOI: 10.1126/science.1112680

Research Articles

The Genome of the Kinetoplastid Parasite, Leishmania major

Alasdair C. Ivens,1* Christopher S. Peacock,1 Elizabeth A. Worthey,2 Lee Murphy,1 Gautam Aggarwal,2 Matthew Berriman,1 Ellen Sisk,2 Marie-Adele Rajandream,1 Ellen Adlem,1 Rita Aert,3 Atashi Anupama,2 Zina Apostolou,4 Philip Attipoe,2 Nathalie Bason,1 Christopher Bauser,5 Alfred Beck,6 Stephen M. Beverley,7 Gabriella Bianchettin,8 Katja Borzym,6 Gordana Bothe,5 Carlo V. Bruschi,8,9 Matt Collins,1 Eithon Cadag,2 Laura Ciarloni,8 Christine Clayton,10 Richard M. R. Coulson,11 Ann Cronin,1 Angela K. Cruz,12 Robert M. Davies,1 Javier De Gaudenzi,13 Deborah E. Dobson,7 Andreas Duesterhoeft,14 Gholam Fazelina,2 Nigel Fosker,1 Alberto Carlos Frasch,13 Audrey Fraser,1 Monika Fuchs,4 Claudia Gabel,4 Arlette Goble,1 André Goffeau,15 David Harris,1 Christiane Hertz-Fowler,1 Helmut Hilbert,14 David Horn,16 Yiting Huang,2 Sven Klages,6 Andrew Knights,1 Michael Kube,6 Natasha Larke,1 Lyudmila Litvin,2 Angela Lord,1 Tin Louie,2 Marco Marra,17 David Masuy,15 Keith Matthews,18 Shulamit Michaeli,19 Jeremy C. Mottram,20 Silke Müller-Auer,4 Heather Munden,2 Siri Nelson,2 Halina Norbertczak,1 Karen Oliver,1 Susan O'Neil,1 Martin Pentony,2 Thomas M. Pohl,5 Claire Price,1 Bénédicte Purnelle,15 Michael A. Quail,1 Ester Rabbinowitsch,1 Richard Reinhardt,6 Michael Rieger,4 Joel Rinta,2 Johan Robben,3 Laura Robertson,2 Jeronimo C. Ruiz,12 Simon Rutter,1 David Saunders,1 Melanie Schäfer,4 Jacquie Schein,17 David C. Schwartz,21 Kathy Seeger,1 Amber Seyler,2 Sarah Sharp,1 Heesun Shin,17 Dhileep Sivam,2 Rob Squares,1 Steve Squares,1 Valentina Tosato,8 Christy Vogt,2 Guido Volckaert,3 Rolf Wambutt,22 Tim Warren,1 Holger Wedler,14 John Woodward,1 Shiguo Zhou,21 Wolfgang Zimmermann,22 Deborah F. Smith,23 Jenefer M. Blackwell,24 Kenneth D. Stuart,2,25 Bart Barrell,1 Peter J. Myler2,25,26*

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II–directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.

1 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
2 Seattle Biomedical Research Institute (SBRI), 307 Westlake Avenue North, Seattle, WA 98109–2591, USA.
3 Laboratory of Gene Technology, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven, Belgium.
4 GENOTYPE GmbH, Angelhofweg 39, D-69259 Wilhelmsfeld, Germany.
5 GATC Biotech AG, Jakob-Stadler-Platz 7, 78467 Konstanz, Germany.
6 Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, D-14195, Berlin (Dahlem), Germany.
7 Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110–1093, USA.
8 Genomics Group–Genetics Laboratory, Department of Biology, University of Trieste, P. le Valmaura, 9, I-34148 Trieste, Italy.
9 International Centre for Genetic Engineering and Biotechnology, AREA Science Park–W, Padriciano 99, I-34012 Trieste, Italy.
10 Zentrum für Molekulare Biologie, Im Neueheimer Feld 282, D69120 Heidelberg, Germany.
11 European Molecular Biology Laboratory–European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
12 Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Av. Bandeirantes, 3900, CEP 14049–900 Ribeirao Preto, Sao Paulo, Brazil.
13 Instituto de Investigaciones Biotecnologicas (IIB-INTECH), University of San Martin and National Research Council (CONICET), Av. Gral Paz 5445, 1650 Buenos Aires, Argentina.
14 QIAGEN GmbH, QIAGEN Strasse 1, 40724 Hilden, Germany.
15 Unité de Biochimie Physiologique, Institut des Sciences de la Vie, Université Catholique de Louvain, place Croix du Sud, 2/20, 1348 Louvain-la-Neuve, Belgium.
16 London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
17 Genome Sequence Centre, British Columbia Cancer Agency Genome Sciences Centre, 600 West 10th Avenue, Vancouver, BC V5Z-4E6, Canada.
18 Institute for Immunology and Infection Research, University of Edinburgh, The King's Buildings, West Mains Road, Edinburgh EH9 3JT, UK.
19 Faculty of Life Sciences, BarIlan University, Ramat-Gan, 52900 Israel.
20 Wellcome Centre for Molecular Parasitology, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK.
21 UW Biotechnology Center, Laboratory for Molecular and Computational Genomics, University of Wisconsin-Madison, 425 Henry Mall, Madison, WI 53706, USA.
22 Agowa GmbH, Glienicker Weg 185, D-12489 Berlin, Germany.
23 Immunology and Infection Unit, Department of Biology, University of York, York YO10 5YW, UK.
24 Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK.
25 Department of Pathobiology, University of Washington, Seattle, WA 98195, USA.
26 Division of Biomedical and Health Informatics, University of Washington, Seattle, WA 98195, USA.

* To whom correspondence should be addressed. E-mail: alicat{at}sanger.ac.uk (A.C.I.), peter.myler{at}sbri.org (P.J.M.)

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Homologs of Mitochondrial Transcription Factor B, Sparsely Distributed Within the Eukaryotic Radiation, Are Likely Derived from the Dimethyladenosine Methyltransferase of the Mitochondrial Endosymbiont.
T. E. Shutt and M. W. Gray (2006)
Mol. Biol. Evol. 23, 1169-1179
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A bifunctional tRNA import receptor from Leishmania mitochondria.
S. Goswami, G. Dhar, S. Mukherjee, B. Mahata, S. Chatterjee, P. Home, and S. Adhya (2006)
PNAS 103, 8354-8359
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Dual targeting of a single tRNATrp requires two different tryptophanyl-tRNA synthetases in Trypanosoma brucei.
F. Charriere, S. Helgadottir, E. K. Horn, D. Soll, and A. Schneider (2006)
PNAS 103, 6847-6852
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Virulence of Leishmania major in macrophages and mice requires the gluconeogenic enzyme fructose-1,6-bisphosphatase.
T. Naderer, M. A. Ellis, M. F. Sernee, D. P. De Souza, J. Curtis, E. Handman, and M. J. McConville (2006)
PNAS 103, 5502-5507
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A "Holistic" Kinesin Phylogeny Reveals New Kinesin Families and Predicts Protein Functions.
B. Wickstead and K. Gull (2006)
Mol. Biol. Cell 17, 1734-1743
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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
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A Divergent Transcription Factor TFIIB in Trypanosomes Is Required for RNA Polymerase II-Dependent Spliced Leader RNA Transcription and Cell Viability.
J. B. Palenchar, W. Liu, P. M. Palenchar, and V. Bellofatto (2006)
Eukaryot. Cell 5, 293-300
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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
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The two eIF4A helicases in Trypanosoma brucei are functionally distinct..
R. Dhalia, N. Marinsek, C. R. S. Reis, R. Katz, J. R. C. Muniz, N. Standart, M. Carrington, and O. P. de Melo Neto (2006)
Nucleic Acids Res. 34, 2495-2507
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EMBL Nucleotide Sequence Database: developments in 2005.
G. Cochrane, P. Aldebert, N. Althorpe, M. Andersson, W. Baker, A. Baldwin, K. Bates, S. Bhattacharyya, P. Browne, A. van den Broek, et al. (2006)
Nucleic Acids Res. 34, D10-D15
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TcruziDB: an integrated, post-genomics community resource for Trypanosoma cruzi.
F. Aguero, W. Zheng, D. B. Weatherly, P. Mendes, and J. C. Kissinger (2006)
Nucleic Acids Res. 34, D428-D431
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RNA-Binding Domain Proteins in Kinetoplastids: a Comparative Analysis.
J. De Gaudenzi, A. C. Frasch, and C. Clayton (2005)
Eukaryot. Cell 4, 2106-2114
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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
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The Translational Efficiencies of the Two Leishmania infantum HSP70 mRNAs, Differing in Their 3'-Untranslated Regions, Are Affected by Shifts in the Temperature of Growth through Different Mechanisms.
C. Folgueira, L. Quijada, M. Soto, D. R. Abanades, C. Alonso, and J. M. Requena (2005)
J. Biol. Chem. 280, 35172-35183
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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
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The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas Disease.
N. M. El-Sayed, P. J. Myler, D. C. Bartholomeu, D. Nilsson, G. Aggarwal, A.-N. Tran, E. Ghedin, E. A. Worthey, A. L. Delcher, G. Blandin, et al. (2005)
Science 309, 409-415
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The Genome of the African Trypanosome Trypanosoma brucei.
M. Berriman, E. Ghedin, C. Hertz-Fowler, G. Blandin, H. Renauld, D. C. Bartholomeu, N. J. Lennard, E. Caler, N. E. Hamlin, B. Haas, et al. (2005)
Science 309, 416-422
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