Department of Microbiology, Immunology & Tropical Medicine, and Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, D. C., United States of America.
PLoS Negl Trop Dis. 2012;6(6):e1686. doi: 10.1371/journal.pntd.0001686. Epub 2012 Jun 12.
Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of primordial germ cells and the germ line in the Metazoa. Using bioinformatics, 33 putative DEAD-box RNA helicases exhibiting conserved motifs that characterize helicases of this family were identified in the S. mansoni genome. Moreover, three of the helicases exhibited vasa-like sequences; phylogenetic analysis confirmed the three vasa-like genes-termed Smvlg1, Smvlg2, and Smvlg3-were members of the Vasa/PL10 DEAD-box subfamily. Transcripts encoding Smvlg1, Smvlg2, and Smvlg3 were cloned from cDNAs from mixed sex adult worms, and quantitative real time PCR revealed their presence in developmental stages of S. mansoni with elevated expression in sporocysts, adult females, eggs, and miracidia, with strikingly high expression in the undeveloped egg. Whole mount in situ hybridization (WISH) analysis revealed that Smvlg1, Smvlg2 and Smvlg3 were transcribed in the posterior ovary where the oocytes mature. Germ cell specific expression of schistosome vasa-like genes should provide an informative landmark for germ line transgenesis of schistosomes, etiologic agents of major neglected tropical diseases.
基因组序列可用于日本血吸虫、曼氏血吸虫和埃及血吸虫等人体血液吸虫。功能基因组学方法可以帮助鉴定这些新描述的血吸虫基因的作用和重要性。转基因技术已在模式物种中建立,用于功能基因组学,可以导致获得或丧失功能,促进基于载体的 RNA 干扰,并代表插入诱变筛选的有效正向遗传学工具。如果能够可靠地定位培养的血吸虫中的生殖细胞,那么常规转基因在血吸虫中的进展可能会加快。Vasa 是 ATP 依赖性 DEAD 盒 RNA 解旋酶家族的成员,是原生生殖细胞和后生动物中生殖系的典型标志物。使用生物信息学,在曼氏血吸虫基因组中鉴定出 33 个推定的 DEAD 盒 RNA 解旋酶,这些解旋酶具有该家族解旋酶的保守基序。此外,其中 3 个解旋酶表现出类似于 vasa 的序列;系统发育分析证实,这 3 个类似于 vasa 的基因——称为 Smvlg1、Smvlg2 和 Smvlg3——是 Vasa/PL10 DEAD 盒亚家族的成员。从混合性别成虫 cDNA 中克隆了编码 Smvlg1、Smvlg2 和 Smvlg3 的转录本,定量实时 PCR 显示它们存在于曼氏血吸虫的发育阶段,在孢子囊中、雌性成虫、卵和毛蚴中表达升高,在未发育的卵中表达极高。整体原位杂交 (WISH) 分析显示,Smvlg1、Smvlg2 和 Smvlg3 在卵母细胞成熟的后卵巢中转录。血吸虫类似 vasa 的基因的生殖细胞特异性表达应为血吸虫生殖系转基因提供一个信息性标记,血吸虫是主要被忽视的热带病的病原体。