Draft Genome of the Filarial Nematode Parasite Brugia malayi

Elodie Ghedin,^1,2# Shiliang Wang,² David Spiro,² Elisabet Caler,² Qi Zhao,² Jonathan Crabtree,² Jonathan E. Allen,^2* Arthur L. Delcher,² David B. Guiliano,³ Diego Miranda-Saavedra,⁴ Samuel V. Angiuoli,² Todd Creasy,² Paolo Amedeo,² Brian Haas,² Najib M. El-Sayed,² Jennifer R. Wortman,² Tamara Feldblyum,² Luke Tallon,² Michael Schatz,² Martin Shumway,² Hean Koo,² Steven L. Salzberg,² Seth Schobel,² Mihaela Pertea,² Mihai Pop,² Owen White,² Geoffrey J. Barton,⁴ Clotilde K. S. Carlow,⁵ Michael J. Crawford,⁶ Jennifer Daub,^7|| Matthew W. Dimmic,⁶ Chris F. Estes,⁸ Jeremy M. Foster,⁵ Mehul Ganatra,⁵ William F. Gregory,⁷ Nicholas M. Johnson,⁹ Jinming Jin,¹⁰ Richard Komuniecki,¹¹ Ian Korf,¹² Sanjay Kumar,⁵ Sandra Laney,¹³ Ben-Wen Li,¹⁴ Wen Li,¹³ Tim H. Lindblom,⁸ Sara Lustigman,¹⁵ Dong Ma,⁵ Claude V. Maina,⁵ David M. A. Martin,⁴ James P. McCarter,^6,16 Larry McReynolds,¹⁰ Makedonka Mitreva,¹⁶ Thomas B. Nutman,¹⁷ John Parkinson,¹⁸ José M. Peregrín-Alvarez,¹ Catherine Poole,⁵ Qinghu Ren,² Lori Saunders,¹³ Ann E. Sluder,¹⁹ Katherine Smith,¹¹ Mario Stanke,²⁰ Thomas R. Unnasch,²¹ Jenna Ware,⁵ Aguan D. Wei,²² Gary Weil,¹⁴ Deryck J. Williams,⁷ Yinhua Zhang,⁵ Steven A. Williams,¹³ Claire Fraser-Liggett,^2¶ Barton Slatko,⁵ Mark L. Blaxter,⁷ Alan L. Scott²³

Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the 90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict 11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during 350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.

¹ Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
² The Institute for Genomic Research (TIGR) and the J. Craig Venter Institute, 9712 Medical Center Drive, Rockville, MD 20850, USA.
³ Division of Cell and Molecular Biology, Biochemistry Building, Imperial College London, Exhibition Road, South Kensington, London, SW7 2AZ, UK.
⁴ School of Life Sciences Research, University of Dundee, Dow Street, Dundee, DD1 5EH, UK.
⁵ Division of Parasitology, New England BioLabs, Inc., 240 County Road, Ipswich, MA 01938, USA.
⁶ Divergence, Inc., 893 North Warson Road, St. Louis, MO 63141, USA.
⁷ Institute of Evolutionary Biology and Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh EH9 3JT, UK.
⁸ Division of Science, Lyon College, 2300 Highland Road, Batesville, AR 72501, USA.
⁹ School of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT 0200, Australia.
¹⁰ Division of RNA Biology, New England Biolabs, Inc., 240 County Road, Ipswich, MA 01938, USA.
¹¹ Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606–3390, USA.
¹² Genome Center, Section of Molecular Biology, Division of Biological Sciences, University of California at Davis, Davis, CA 95616, USA.
¹³ Clark Science Center, Smith College, Northampton, MA 01063, USA.
¹⁴ Infectious Diseases Division, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
¹⁵ Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10021, USA.
¹⁶ Genome Sequencing Center, Washington University School of Medicine, 4444 Forest Park Avenue, St. Louis, MO 63108, USA.
¹⁷ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 6610 Rockledge Drive, Bethesda, MD 20892–6612, USA.
¹⁸ Program in Molecular Structure and Function, Hospital for Sick Children, TMDT Building, 101 College Street, 15th Floor, East Tower, Toronto, ON, Canada, M5G 1L7.
¹⁹ Cambria Biosciences, 8A Henshaw Street, Woburn, MA 01801, USA.
²⁰ Department of Bioinformatics, University of Göttingen, Goldschmidtstrasse 1, 37077 Göttingen, Germany.
²¹ Division of Geographic Medicine, University of Alabama at Birmingham, BBRB 203, 1530 Third Avenue South, Birmingham, AL 35294–2170, USA.
²² Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
²³ Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe, Baltimore, MD 21205, USA.

^* Present address: Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550, USA.

Present address: Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.

Present address: Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK.

Present address: Department of Cell Biology and Molecular Genetics, 2105 H. J. Patterson Hall, and Center for Bioinformatics and Computational Biology, 3115 Biomolecular Sciences Building, University of Maryland, College Park, MD 20742, USA.

^|| Present address: The Wellcome Trust Sanger Institute, Hinxton Genome Campus, Cambridge CB10 1SA, UK.

^¶ Present address: Institute for Genome Sciences, University of Maryland School of Medicine, 800 West Baltimore Street, Baltimore, MD 21201, USA.

^# To whom correspondence should be addressed. E-mail: GhedinE{at}dom.pitt.edu