科学家测出了象皮病的病原体马来丝虫(Brugia malayi)的基因组序列,这一成果可能有助于开发针对该病的新药。
由英国、美国和加拿大科学家开展的这项研究发表在了9月21日的《科学》杂志上。为了发现马来丝虫基因组中与象皮病相关的基因,他们比较了马来丝虫和其他两种线虫的基因组。
象皮病(淋巴丝虫病)是一种蚊媒疾病,它是由包括马来丝虫在内的几种线虫导致的。根据世界卫生组织的数据,全世界有1亿人受到该病影响,大部分生活在发展中国家。
一旦感染更该病,丝虫就会生活在人体的淋巴结中,导致肢体和外生殖器肿胀和畸形。
尽管现有疗法很有效,但是它们的疗程很长,而患者坚持服药的比率通常较低,这就降低了这些疗法的效果。治疗药物有毒副作用,也有耐药性病例的报道,这凸显了对新疗法的需求。
这组科学家发现了马来丝虫的1.15万个编码蛋白质的基因。该研究的第一作者、美国匹兹堡医学院的Elodie Ghedin告诉本网站说,他们的研究组在比较马来丝虫和此前测出的该寄生虫的一些基因序列时吃惊地发现,大约有20%到30%的序列不匹配。
由这些新发现的基因编码而成的蛋白质似乎与已知的免疫调节蛋白(免疫系统的调节因子)类似,这表明它们参与了让宿主的免疫系统失效的工作,从而确保寄生虫不被发现。
Ghedin说:“这种寄生虫可以在宿主体内生存数年而不必然导致疾病。事实上,被感染个体表现出的疾病越少,他们体内的寄生虫就越多。如今我们知道了这些人类没有的基因,我们就可以把它们作为靶点控制疾病。”
她还说,知道了这类此前未知的免疫抑制因子,也可能用于器官移植和帮助治疗自体免疫疾病。(科学与发展网)
原始出处:
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 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@dom.pitt.edu