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The Genome of the African Trypanosome Trypanosoma brucei
Matthew Berriman,1*Elodie Ghedin,2,3Christiane Hertz-Fowler,1Gaëlle Blandin,2Hubert Renauld,1Daniella C. Bartholomeu,2Nicola J. Lennard,1Elisabet Caler,2Nancy E. Hamlin,1Brian Haas,2Ulrike Böhme,1Linda Hannick,2Martin A. Aslett,1Joshua Shallom,2Lucio Marcello,4Lihua Hou,2Bill Wickstead,5U. Cecilia M. Alsmark,6Claire Arrowsmith,1Rebecca J. Atkin,1Andrew J. Barron,1Frederic Bringaud,7Karen Brooks,1Mark Carrington,8Inna Cherevach,1Tracey-Jane Chillingworth,1Carol Churcher,1Louise N. Clark,1Craig H. Corton,1Ann Cronin,1Rob M. Davies,1Jonathon Doggett,1Appolinaire Djikeng,2Tamara Feldblyum,2Mark C. Field,9Audrey Fraser,1Ian Goodhead,1Zahra Hance,1David Harper,1Barbara R. Harris,1Heidi Hauser,1Jessica Hostetler,2Al Ivens,1Kay Jagels,1David Johnson,1Justin Johnson,2Kristine Jones,2Arnaud X. Kerhornou,1Hean Koo,2Natasha Larke,1Scott Landfear,10Christopher Larkin,2Vanessa Leech,9Alexandra Line,1Angela Lord,1Annette MacLeod,4Paul J. Mooney,1Sharon Moule,1David M. A. Martin,11Gareth W. Morgan,12Karen Mungall,1Halina Norbertczak,1Doug Ormond,1Grace Pai,2Chris S. Peacock,1Jeremy Peterson,2Michael A. Quail,1Ester Rabbinowitsch,1Marie-Adele Rajandream,1Chris Reitter,9Steven L. Salzberg,2Mandy Sanders,1Seth Schobel,2Sarah Sharp,1Mark Simmonds,1Anjana J. Simpson,2Luke Tallon,2C. Michael R. Turner,13Andrew Tait,4Adrian R. Tivey,1Susan Van Aken,2Danielle Walker,1David Wanless,2Shiliang Wang,2Brian White,1Owen White,2Sally Whitehead,1John Woodward,1Jennifer Wortman,2Mark D. Adams,14T. Martin Embley,6Keith Gull,5Elisabetta Ullu,15J. David Barry,4Alan H. Fairlamb,11Fred Opperdoes,16Barclay G. Barrell,1John E. Donelson,17Neil Hall,1Claire M. Fraser,2Sara E. Melville,9Najib M. El-Sayed2,3*
African trypanosomes cause human sleeping sickness and livestocktrypanosomiasis in sub-Saharan Africa. We present the sequenceand analysis of the 11 megabase-sized chromosomes of Trypanosomabrucei. The 26-megabase genome contains 9068 predicted genes,including 900 pseudogenes and 1700 T. bruceispecificgenes. Large subtelomeric arrays contain an archive of 806 variantsurface glycoprotein (VSG) genes used by the parasite to evadethe mammalian immune system. Most VSG genes are pseudogenes,which may be used to generate expressed mosaic genes by ectopicrecombination. Comparisons of the cytoskeleton and endocytictrafficking systems with those of humans and other eukaryoticorganisms reveal major differences. A comparison of metabolicpathways encoded by the genomes of T. brucei, T. cruzi, andLeishmania major reveals the least overall metabolic capabilityin T. brucei and the greatest in L. major. Horizontal transferof genes of bacterial origin has contributed to some of themetabolic differences in these parasites, and a number of novelpotential 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 972393098, 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 065208022, 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.
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.)
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