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.
Science Signaling - Call for Papers

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 15 July 2005:
Vol. 309. no. 5733, pp. 416 - 422
DOI: 10.1126/science.1112642

Research Articles

The Genome of the African Trypanosome Trypanosoma brucei

Matthew Berriman,1* Elodie Ghedin,2,3 Christiane Hertz-Fowler,1 Gaëlle Blandin,2 Hubert Renauld,1 Daniella C. Bartholomeu,2 Nicola J. Lennard,1 Elisabet Caler,2 Nancy E. Hamlin,1 Brian Haas,2 Ulrike Böhme,1 Linda Hannick,2 Martin A. Aslett,1 Joshua Shallom,2 Lucio Marcello,4 Lihua Hou,2 Bill Wickstead,5 U. Cecilia M. Alsmark,6 Claire Arrowsmith,1 Rebecca J. Atkin,1 Andrew J. Barron,1 Frederic Bringaud,7 Karen Brooks,1 Mark Carrington,8 Inna Cherevach,1 Tracey-Jane Chillingworth,1 Carol Churcher,1 Louise N. Clark,1 Craig H. Corton,1 Ann Cronin,1 Rob M. Davies,1 Jonathon Doggett,1 Appolinaire Djikeng,2 Tamara Feldblyum,2 Mark C. Field,9 Audrey Fraser,1 Ian Goodhead,1 Zahra Hance,1 David Harper,1 Barbara R. Harris,1 Heidi Hauser,1 Jessica Hostetler,2 Al Ivens,1 Kay Jagels,1 David Johnson,1 Justin Johnson,2 Kristine Jones,2 Arnaud X. Kerhornou,1 Hean Koo,2 Natasha Larke,1 Scott Landfear,10 Christopher Larkin,2 Vanessa Leech,9 Alexandra Line,1 Angela Lord,1 Annette MacLeod,4 Paul J. Mooney,1 Sharon Moule,1 David M. A. Martin,11 Gareth W. Morgan,12 Karen Mungall,1 Halina Norbertczak,1 Doug Ormond,1 Grace Pai,2 Chris S. Peacock,1 Jeremy Peterson,2 Michael A. Quail,1 Ester Rabbinowitsch,1 Marie-Adele Rajandream,1 Chris Reitter,9 Steven L. Salzberg,2 Mandy Sanders,1 Seth Schobel,2 Sarah Sharp,1 Mark Simmonds,1 Anjana J. Simpson,2 Luke Tallon,2 C. Michael R. Turner,13 Andrew Tait,4 Adrian R. Tivey,1 Susan Van Aken,2 Danielle Walker,1 David Wanless,2 Shiliang Wang,2 Brian White,1 Owen White,2 Sally Whitehead,1 John Woodward,1 Jennifer Wortman,2 Mark D. Adams,14 T. Martin Embley,6 Keith Gull,5 Elisabetta Ullu,15 J. David Barry,4 Alan H. Fairlamb,11 Fred Opperdoes,16 Barclay G. Barrell,1 John E. Donelson,17 Neil Hall,1{dagger} Claire M. Fraser,2 Sara E. Melville,9 Najib M. El-Sayed2,3*

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 Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ~900 pseudogenes and ~1700 T. brucei–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 T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. 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.

1 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
2 The Institute for Genomic Research, Rockville, MD 20850, USA.
3 Department of Microbiology and Tropical Medicine, George Washington University, Washington, DC 20052, USA.
4 Wellcome Centre for Molecular Parasitology, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK.
5 Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
6 School of Biology, Devonshire Building, University of Newcastle upon Tyne, Newcastle NE1 7RU, UK.
7 Laboratoire de Génomique Fonctionnelle des Trypanosomatides, Université Victor Segalen Bordeaux II, UMR-5162 CNRS, 33076 Bordeaux cedex, France.
8 Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
9 Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
10 Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mail Code L474, Portland, OR 97239–3098, USA.
11 School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, UK.
12 Department of Biological Sciences, Imperial College, London SW7 2AY, UK.
13 Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
14 Department of Genetics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
15 Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208022, New Haven, CT 06520–8022, USA.
16 Christian de Duve Institute of Cellular Pathology and Catholic University of Louvain, Avenue Hippocrate 74-75, B-1200 Brussels, Belgium.
17 Department of Biochemistry, University of Iowa, Iowa City, IA 52242, USA.

{dagger} Present address: Institute for Genomic Research, Rockville, MD 20850, USA.

* To whom correspondence should be addressed. E-mail: mb4{at}sanger.ac.uk (M.B.); nelsayed{at}tigr.org (N.M.E.-S.)

Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Trypanosoma brucei Mitochondrial Ribosomes: Affinity Purification and Component Identification by Mass Spectrometry.
A. Zikova, A. K. Panigrahi, R. A. Dalley, N. Acestor, A. Anupama, Y. Ogata, P. J. Myler, and K. Stuart (2008)
Mol. Cell. Proteomics 7, 1286-1296
   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 »
A Haptoglobin-Hemoglobin Receptor Conveys Innate Immunity to Trypanosoma brucei in Humans.
B. Vanhollebeke, G. De Muylder, M. J. Nielsen, A. Pays, P. Tebabi, M. Dieu, M. Raes, S. K. Moestrup, and E. Pays (2008)
Science 320, 677-681
   Abstract »    Full Text »    PDF »
Deadenylation-independent stage-specific mRNA degradation in Leishmania.
S. Haile, A. Dupe, and B. Papadopoulou (2008)
Nucleic Acids Res. 36, 1634-1644
   Abstract »    Full Text »    PDF »
Mitochondrial Complexes in Trypanosoma brucei: A Novel Complex and a Unique Oxidoreductase Complex.
A. K. Panigrahi, A. Zikova, R. A. Dalley, N. Acestor, Y. Ogata, A. Anupama, P. J. Myler, and K. D. Stuart (2008)
Mol. Cell. Proteomics 7, 534-545
   Abstract »    Full Text »    PDF »
RNA Polymerase Transcription Machinery in Trypanosomes.
A. Das, M. Banday, and V. Bellofatto (2008)
Eukaryot. Cell 7, 429-434
   Full Text »    PDF »
Intraflagellar Transport and Functional Analysis of Genes Required for Flagellum Formation in Trypanosomes.
S. Absalon, T. Blisnick, L. Kohl, G. Toutirais, G. Dore, D. Julkowska, A. Tavenet, and P. Bastin (2008)
Mol. Biol. Cell 19, 929-944
   Abstract »    Full Text »    PDF »
Adenosine Kinase Mediates High Affinity Adenosine Salvage in Trypanosoma brucei.
M. Vodnala, A. Fijolek, R. Rofougaran, M. Mosimann, P. Maser, and A. Hofer (2008)
J. Biol. Chem. 283, 5380-5388
   Abstract »    Full Text »    PDF »
Superinfection as a driver of genomic diversification in antigenically variant pathogens.
J. E. Futse, K. A. Brayton, M. J. Dark, D. P. Knowles Jr., and G. H. Palmer (2008)
PNAS 105, 2123-2127
   Abstract »    Full Text »    PDF »
Structure of a Glycosylphosphatidylinositol-anchored Domain from a Trypanosome Variant Surface Glycoprotein.
N. G. Jones, D. Nietlispach, R. Sharma, D. F. Burke, I. Eyres, M. Mues, H. R. Mott, and M. Carrington (2008)
J. Biol. Chem. 283, 3584-3593
   Abstract »    Full Text »    PDF »
Control and Regulation of Gene Expression: QUANTITATIVE ANALYSIS OF THE EXPRESSION OF PHOSPHOGLYCERATE KINASE IN BLOODSTREAM FORM TRYPANOSOMA BRUCEI.
J. R. Haanstra, M. Stewart, V.-D. Luu, A. van Tuijl, H. V. Westerhoff, C. Clayton, and B. M. Bakker (2008)
J. Biol. Chem. 283, 2495-2507
   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 »
The Role of the Mitochondrial Glycine Cleavage Complex in the Metabolism and Virulence of the Protozoan Parasite Leishmania major.
D. A. Scott, S. M. Hickerson, T. J. Vickers, and S. M. Beverley (2008)
J. Biol. Chem. 283, 155-165
   Abstract »    Full Text »    PDF »
Adenosine Kinase of Trypanosoma brucei and Its Role in Susceptibility to Adenosine Antimetabolites.
A. Luscher, P. Onal, A.-M. Schweingruber, and P. Maser (2007)
Antimicrob. Agents Chemother. 51, 3895-3901
   Abstract »    Full Text »    PDF »
Maintenance of Antibody to Pathogen Epitopes Generated by Segmental Gene Conversion Is Highly Dynamic during Long-Term Persistent Infection.
Y. Zhuang, J. E. Futse, W. C. Brown, K. A. Brayton, and G. H. Palmer (2007)
Infect. Immun. 75, 5185-5190
   Abstract »    Full Text »    PDF »
Plasmodium falciparum Sir2: an Unusual Sirtuin with Dual Histone Deacetylase and ADP-Ribosyltransferase Activity.
C. J. Merrick and M. T. Duraisingh (2007)
Eukaryot. Cell 6, 2081-2091
   Abstract »    Full Text »    PDF »
Small Trypanosome RNA-Binding Proteins TbUBP1 and TbUBP2 Influence Expression of F-Box Protein mRNAs in Bloodstream Trypanosomes.
C. Hartmann, C. Benz, S. Brems, L. Ellis, V.-D. Luu, M. Stewart, I. D'Orso, C. Busold, K. Fellenberg, A. C. C. Frasch, et al. (2007)
Eukaryot. Cell 6, 1964-1978
   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 »
Tousled-like kinase in a microbial eukaryote regulates spindle assembly and S-phase progression by interacting with Aurora kinase and chromatin assembly factors.
Z. Li, S. Gourguechon, and C. C. Wang (2007)
J. Cell Sci. 120, 3883-3894
   Abstract »    Full Text »    PDF »
A high-resolution solution structure of a trypanosomatid FYVE domain.
H. D.T. Mertens, J. M. Callaghan, J. D. Swarbrick, M. J. McConville, and P. R. Gooley (2007)
Protein Sci. 16, 2552-2559
   Abstract »    Full Text »    PDF »
Pentatricopeptide Repeat Proteins in Trypanosoma brucei Function in Mitochondrial Ribosomes.
M. Pusnik, I. Small, L. K. Read, T. Fabbro, and A. Schneider (2007)
Mol. Cell. Biol. 27, 6876-6888
   Abstract »    Full Text »    PDF »
Ku Heterodimer-Independent End Joining in Trypanosoma brucei Cell Extracts Relies upon Sequence Microhomology.
P. Burton, D. J. McBride, J. M. Wilkes, J. D. Barry, and R. McCulloch (2007)
Eukaryot. Cell 6, 1773-1781
   Abstract »    Full Text »    PDF »
The de Novo Synthesis of GDP-fucose Is Essential for Flagellar Adhesion and Cell Growth in Trypanosoma brucei.
D. C. Turnock, L. Izquierdo, and M. A. J. Ferguson (2007)
J. Biol. Chem. 282, 28853-28863
   Abstract »    Full Text »    PDF »
Active RNA Polymerase I of Trypanosoma brucei Harbors a Novel Subunit Essential for Transcription.
T. N. Nguyen, B. Schimanski, and A. Gunzl (2007)
Mol. Cell. Biol. 27, 6254-6263
   Abstract »    Full Text »    PDF »
Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure.
L. Marcello and J. D. Barry (2007)
Genome Res. 17, 1344-1352
   Abstract »    Full Text »    PDF »
Centrin1 Is Required for Organelle Segregation and Cytokinesis in Trypanosoma brucei.
A. Selvapandiyan, P. Kumar, J. C. Morris, J. L. Salisbury, C. C. Wang, and H. L. Nakhasi (2007)
Mol. Biol. Cell 18, 3290-3301
   Abstract »    Full Text »    PDF »
Cyclic Nucleotide Signaling Mechanisms in Trypanosomes: Possible Targets for Therapeutic Agents.
S. Laxman and J. A. Beavo (2007)
Mol. Interv. 7, 203-215
   Abstract »    Full Text »    PDF »
The Proteome of the Mouse Photoreceptor Sensory Cilium Complex.
Q. Liu, G. Tan, N. Levenkova, T. Li, E. N. Pugh Jr., J. J. Rux, D. W. Speicher, and E. A. Pierce (2007)
Mol. Cell. Proteomics 6, 1299-1317
   Abstract »    Full Text »    PDF »
Sugar Nucleotide Pools of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major.
D. C. Turnock and M. A. J. Ferguson (2007)
Eukaryot. Cell 6, 1450-1463
   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.
R. L. Barnes and R. McCulloch (2007)
Nucleic Acids Res. 35, 3478-3493
   Abstract »    Full Text »    PDF »
Parasite-intrinsic factors can explain ordered progression of trypanosome antigenic variation.
K. A. Lythgoe, L. J. Morrison, A. F. Read, and J. D. Barry (2007)
PNAS 104, 8095-8100
   Abstract »    Full Text »    PDF »
An Essential Cell Cycle-regulated Nucleolar Protein Relocates to the Mitotic Spindle Where It Is Involved in Mitotic Progression in Trypanosoma brucei.
N. Boucher, D. Dacheux, C. Giroud, and T. Baltz (2007)
J. Biol. Chem. 282, 13780-13790
   Abstract »    Full Text »    PDF »
The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase.
Z. Yu, P.-A. Genest, B. ter Riet, K. Sweeney, C. DiPaolo, R. Kieft, E. Christodoulou, A. Perrakis, J. M. Simmons, R. P. Hausinger, et al. (2007)
Nucleic Acids Res. 35, 2107-2115
   Abstract »    Full Text »    PDF »
Spliced Leader RNA Gene Transcription in Trypanosoma brucei Requires Transcription Factor TFIIH.
J. H. Lee, T. N. Nguyen, B. Schimanski, and A. Gunzl (2007)
Eukaryot. Cell 6, 641-649
   Abstract »    Full Text »    PDF »
Glutathionylation of Trypanosomal Thiol Redox Proteins.
J. Melchers, N. Dirdjaja, T. Ruppert, and R. L. Krauth-Siegel (2007)
J. Biol. Chem. 282, 8678-8694
   Abstract »    Full Text »    PDF »
Distinct roles of haptoglobin-related protein and apolipoprotein L-I in trypanolysis by human serum.
B. Vanhollebeke, M. J. Nielsen, Y. Watanabe, P. Truc, L. Vanhamme, K. Nakajima, S. K. Moestrup, and E. Pays (2007)
PNAS 104, 4118-4123
   Abstract »    Full Text »    PDF »
Cholesterol import fails to prevent catalyst-based inhibition of ergosterol synthesis and cell proliferation of Trypanosoma brucei.
W. Zhou, G. A. M. Cross, and W. D. Nes (2007)
J. Lipid Res. 48, 665-673
   Abstract »    Full Text »    PDF »
Selection for Simple Major Surface Protein 2 Variants during Anaplasma marginale Transmission to Immunologically Naive Animals.
G. H. Palmer, J. E. Futse, C. K. Leverich, D. P. Knowles Jr., F. R. Rurangirwa, and K. A. Brayton (2007)
Infect. Immun. 75, 1502-1506
   Abstract »    Full Text »    PDF »
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 »
Sequencing and analysis of chromosome 1 of Eimeria tenella reveals a unique segmental organization.
K.-H. Ling, M.-A. Rajandream, P. Rivailler, A. Ivens, S.-J. Yap, A. M.B.N. Madeira, K. Mungall, K. Billington, W.-Y. Yee, A. T. Bankier, et al. (2007)
Genome Res. 17, 311-319
   Abstract »    Full Text »    PDF »
Trypanosoma brucei ARF1 Plays a Central Role in Endocytosis and Golgi-Lysosome Trafficking.
H. P. Price, M. Stark, and D. F. Smith (2007)
Mol. Biol. Cell 18, 864-873
   Abstract »    Full Text »    PDF »
Bioinformatic Identification of Tandem Repeat Antigens of the Leishmania donovani Complex.
Y. Goto, R. N. Coler, and S. G. Reed (2007)
Infect. Immun. 75, 846-851
   Abstract »    Full Text »    PDF »
VectorBase: a home for invertebrate vectors of human pathogens.
D. Lawson, P. Arensburger, P. Atkinson, N. J. Besansky, R. V. Bruggner, R. Butler, K. S. Campbell, G. K. Christophides, S. Christley, E. Dialynas, et al. (2007)
Nucleic Acids Res. 35, D503-D505
   Abstract »    Full Text »    PDF »
Identification and Stage-specific Association with the Translational Apparatus of TbZFP3, a CCCH Protein That Promotes Trypanosome Life-cycle Development.
A. Paterou, P. Walrad, P. Craddy, K. Fenn, and K. Matthews (2006)
J. Biol. Chem. 281, 39002-39013
   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 »
Roles for the Trypanosoma brucei P2 Transporter in DB75 Uptake and Resistance.
C. A. Lanteri, M. L. Stewart, J. M. Brock, V. P. Alibu, S. R. Meshnick, R. R. Tidwell, and M. P. Barrett (2006)
Mol. Pharmacol. 70, 1585-1592
   Abstract »    Full Text »    PDF »
Organization of chromosome ends in the rice blast fungus, Magnaporthe oryzae.
C. Rehmeyer, W. Li, M. Kusaba, Y.-S. Kim, D. Brown, C. Staben, R. Dean, and M. Farman (2006)
Nucleic Acids Res. 34, 4685-4701
   Abstract »    Full Text »    PDF »
Post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in Trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage-specific regulatory elements.
M. Mayho, K. Fenn, P. Craddy, S. Crosthwaite, and K. Matthews (2006)
Nucleic Acids Res. 34, 5312-5324
   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 »
Trypanosome IFT mutants provide insight into the motor location for mobility of the flagella connector and flagellar membrane formation.
J. A. Davidge, E. Chambers, H. A. Dickinson, K. Towers, M. L. Ginger, P. G. McKean, and K. Gull (2006)
J. Cell Sci. 119, 3935-3943
   Abstract »    Full Text »    PDF »
Knock-downs of Iron-Sulfur Cluster Assembly Proteins IscS and IscU Down-regulate the Active Mitochondrion of Procyclic Trypanosoma brucei.
O. Smid, E. Horakova, V. Vilimova, I. Hrdy, R. Cammack, A. Horvath, J. Lukes, and J. Tachezy (2006)
J. Biol. Chem. 281, 28679-28686
   Abstract »    Full Text »    PDF »