9月21日Science内容精选

生物谷

象皮病寄生虫的基因组

生物学家制作了第一个寄生蛔虫的基因组草图，它将成为研究象皮病的药物和疫苗的重要工具。Elodie Ghedin和同事测出了马来丝虫(Brugia malayi)的大部分基因组，这个线虫给热带地区发展中国家中上百万人带来患象皮病的威胁，该寄生虫妨碍被感染人的淋巴系统，导致组织肿胀和皮肤变厚。现在，科学家能比较马来丝虫的基因组与独立生存的蛔虫、以及模式生物美丽线虫的基因组，来识别与寄生有关的基因。马来丝虫有一个复杂的生命周期，涉及到两个宿主。这两个宿主的基因组也已测出，研究人员也许能发现寄生虫在这些宿主身上的薄弱环节，从而找到控制该疾病的全新靶标。

英文原文：

Science 21 September 2007:
Vol. 317. no. 5845, pp. 1756 - 1760
DOI: 10.1126/science.1145406

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 ${dagger}$ David B. Guiliano,3 Diego Miranda-Saavedra,4 ${ddagger}$ 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 ${dagger}$ Martin Shumway,2 Hean Koo,2 Steven L. Salzberg,2 ${dagger}$ Seth Schobel,2 Mihaela Pertea,2 ${dagger}$ Mihai Pop,2 ${dagger}$ 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.

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

${ddagger}$ 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.