本期Nature封面上的显微照片(由David Scharf提供)所示为一对交配的曼氏血吸虫,大约放大了265倍,较纤细的雌性出现在雄性的下半部分。
以中国国家人类基因组南方中心为首的联合课题组在本期Nature上报告了日本血吸虫(Schistosoma japonicum)的完整基因组序列,本期Nature同样还发布了一篇曼氏血吸虫(Schistosoma mansoni)测序的文章。两篇文章并列作为本期Nature封面。
曼氏血吸虫和日本血吸虫是引起血吸虫病(也称“裂体血吸虫病”)的三种主要病原体中的两种。世界上共有埃及血吸虫、曼氏血吸虫、日本血吸虫、间插血吸虫、湄公血吸虫等5种寄生于人体的血吸虫。
血吸虫病是一种“被忽视的”热带疾病,影响76个国家的超过2亿人。血吸虫病有急性、慢性之分。急性血吸虫病是在大量感染尾蚴的情况下发生的,病人发病迅猛,可在短期内发展成为晚期或直接进入衰竭状态,导致死亡。慢性血吸虫病一般发展较慢,早期对体力有不同程度的影响,进入晚期后则出现腹水、巨脾、侏儒等症,患者劳动力丧失,甚至造成死亡。
研究显示,血吸虫基因组由近4亿个碱基组成,含有40.1%的重复序列,包括新发现的具有转录活性的反转座子25个。研究工作识别编码基因13469个,其中有首次发现的与血吸虫感染宿主密切相关的弹力蛋白酶(Elastase)。有趣的是,血吸虫与具有同等大小基因组的非寄生生物比较,虽然基因数量相似,但功能基因的组成却有较大差别。一方面它丢失了很多与营养代谢相关的基因,如脂肪酸、氨基酸、胆固醇和性激素合成基因等,这些营养物质必须从哺乳动物宿主获得;另一方面,扩充了许多有利于蛋白消化的酶类基因家族的成员。这一变化充分体现了血吸虫适应寄生生活,与宿主协同进化的重要特性。
研究还揭示,血吸虫像其他多细胞生物一样,具有与发育密切相关的多条重要分子信号途径;血吸虫有原始的中枢神经系统和较为完善的外周感觉神经系统,能接受周围环境发出的声、光、机械振动等信号,有助于攻击宿主并到达营养丰富的器官,如肝脏门静脉、肠静脉等处寄生。血吸虫虽然不像高级哺乳动物那样有下丘脑、垂体、甲状腺、性腺等神经内分泌器官,但是它有类似功能的细胞,编码一些与生长、发育和成熟相关的内分泌激素受体,除了接受本身合成的内分泌激素外,还可以接受宿主的激素作用,甚至形成依赖宿主内分泌激素的寄生状态。
血吸虫能编码并分泌弹力蛋白酶消化宿主如人、牛等皮肤组织而进入体内形成危害。血吸虫在致病过程中,除了编码蛋白酶消化宿主皮肤和血液外,还分泌一些炎症相关分子如前列腺素、聚糖、脂质、自身抗原样蛋白等,这些因子可诱导宿主免疫反应,形成肉芽肿等免疫损伤,导致严重的血吸虫病。
相关研究成果从基因组进化的高度,为认识血吸虫生物学特征、理解宿主与寄生虫的相互关系、拓宽分子寄生虫学和分子进化等研究领域提供了系统的创新知识和分析工具。血吸虫除了有大量与其他物种同源的基因外,还有许多血吸虫特有基因。这也为生物医学界认识血吸虫生物学特征、开发抗血吸虫药物以及研制血吸虫疫苗奠定了理论基础。
这两种血吸虫的基因组是首次被测序的两种扁形虫基因组,所以它们为了解动物演化中的早期事件、尤其是身体模式的确定及组织发育成器官的过程提供了新视角。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 345-351 (16 July 2009) | doi:10.1038/nature08140
The Schistosoma japonicum genome reveals features of host–parasite interplay
The Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium
1 Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, 250 Bi Bo Road, Shanghai 201203, China.
2 School of Life Science/Institutes of Biomedical Sciences, Fudan University, 220 Han Dan Road, Shanghai 200433, China.
3 Shanghai Center for Bioinformation Technology, 100 Qinzhou Road, Shanghai 200235, China.
4 Cheriton School of Computer Science, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.
5 Comparative Genomics Centre/School of Tropical Biology, James Cook University, Townsville, Queensland 4811, Australia.
6 State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Road II, Shanghai 200025, China.
7 National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, 207 Rui Jin Er Road, Shanghai 200025, China.
8 Shanghai Center for Biochip Engineering, 151 Li Bing Road, Shanghai 201203, China.
9 Department of Microbiology, Immunology & Tropical Medicine, George Washington University Medical Center, Ross Hall, Room 448, 2300 I Street, NW, Washington DC 20037, USA.
10 Molecular Parasitology Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland 4006, Australia.
11 Beijing Institute of Genomics, Chinese Academy of Sciences/Beijing Genomics Institute, B-6 Beijing Airport Industrial Zone, Beijing 101300, China.
12 Pathogen Sequencing Unit, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
13 Genome Institute of Singapore, 60 Biopolis Street, Genome #02-01, 138672, Singapore.
14 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation, and derivative works must be licensed under the same or similar licence.
Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.