1. TIGR, 9712 Medical Center Drive, Rockville, Maryland 20850, USA
2. The Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
3. School of Biology, University of Newcastle, King George VI Building, Newcastle upon Tyne NE1 7RU, UK
4. Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA
5. Departments of Internal Medicine & Microbiology, University of Virginia, Charlottesville, Virginia 22908, USA
6. Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
7. Division of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria
8. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
9. Department of Molecular Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany
10. Zoological Institute, University of Kiel, Olshausenstr. 40, 24098 Kiel, Germany
11. School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India
12. Unite de Biologie Cellulaire du Parasitisme, INSERM U389, Institut Pasteur 28, rue du Dr Roux 75724, Paris Cedex 15, France
13. Department of Biochemistry, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata 700054, India
14. Department of Zoology, The Natural History Museum, Cromwell Road, London SW7 5BD, UK
15. Center for Biological Sequence Analysis, Technical University of Denmark, Building 208, DK-2800 Lyngby, Denmark
16. Departments of Internal Medicine, Microbiology, and Immunology, Stanford University School of Medicine, Stanford, California 94305-5107, USA
17. Present address: TIGR, 9712 Medical Center Drive, Rockville, Maryland 20850, USA

Correspondence to: Brendan Loftus¹ Correspondence and requests for materials should be addressed to B.L. (Email: bjloftus@tigr.org).
Scaffold sequences have been deposited in GenBank under the project accession number AAFB00000000. Sequences and annotation are available at http://www.tigr.org/tdb/e2k1/eha1/.

Entamoeba histolytica is an intestinal parasite and the causative agent of amoebiasis, which is a significant source of morbidity and mortality in developing countries¹. Here we present the genome of E. histolytica, which reveals a variety of metabolic adaptations shared with two other amitochondrial protist pathogens: Giardia lamblia and Trichomonas vaginalis. These adaptations include reduction or elimination of most mitochondrial metabolic pathways and the use of oxidative stress enzymes generally associated with anaerobic prokaryotes. Phylogenomic analysis identifies evidence for lateral gene transfer of bacterial genes into the E. histolytica genome, the effects of which centre on expanding aspects of E. histolytica's metabolic repertoire. The presence of these genes and the potential for novel metabolic pathways in E. histolytica may allow for the development of new chemotherapeutic agents. The genome encodes a large number of novel receptor kinases and contains expansions of a variety of gene families, including those associated with virulence. Additional genome features include an abundance of tandemly repeated transfer-RNA-containing arrays, which may have a structural function in the genome. Analysis of the genome provides new insights into the workings and genome evolution of a major human pathogen.

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