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通过比较基因组学鉴定埃及血吸虫和曼氏血吸虫中的G蛋白偶联受体

Identification of G protein-coupled receptors in Schistosoma haematobium and S. mansoni by comparative genomics.

作者信息

Campos Tulio D L, Young Neil D, Korhonen Pasi K, Hall Ross S, Mangiola Stefano, Lonie Andrew, Gasser Robin B

机构信息

Faculty of Veterinary Science, The University of Melbourne, Parkville, Victoria, Australia.

出版信息

Parasit Vectors. 2014 May 27;7:242. doi: 10.1186/1756-3305-7-242.

Abstract

BACKGROUND

Schistosomiasis is a parasitic disease affecting ~200 million people worldwide. Schistosoma haematobium and S. mansoni are two relatively closely related schistosomes (blood flukes), and the causative agents of urogenital and hepatointestinal schistosomiasis, respectively. The availability of genomic, transcriptomic and proteomic data sets for these two schistosomes now provides unprecedented opportunities to explore their biology, host interactions and schistosomiasis at the molecular level. A particularly important group of molecules involved in a range of biological and developmental processes in schistosomes and other parasites are the G protein-coupled receptors (GPCRs). Although GPCRs have been studied in schistosomes, there has been no detailed comparison of these receptors between closely related species. Here, using a genomic-bioinformatic approach, we identified and characterised key GPCRs in S. haematobium and S. mansoni (two closely related species of schistosome).

METHODS

Using a Hidden Markov Model (HMM) and Support Vector Machine (SVM)-based pipeline, we classified and sub-classified GPCRs of S. haematobium and S. mansoni, combined with phylogenetic and transcription analyses.

RESULTS

We identified and classified classes A, B, C and F as well as an unclassified group of GPCRs encoded in the genomes of S. haematobium and S. mansoni. In addition, we characterised ligand-specific subclasses (i.e. amine, peptide, opsin and orphan) within class A (rhodopsin-like).

CONCLUSIONS

Most GPCRs shared a high degree of similarity and conservation, except for members of a particular clade (designated SmGPR), which appear to have diverged between S. haematobium and S. mansoni and might explain, to some extent, some of the underlying biological differences between these two schistosomes. The present set of annotated GPCRs provides a basis for future functional genomic studies of cellular GPCR-mediated signal transduction and a resource for future drug discovery efforts in schistosomes.

摘要

背景

血吸虫病是一种影响全球约2亿人的寄生虫病。埃及血吸虫和曼氏血吸虫是两种关系相对密切的血吸虫(血吸虫),分别是泌尿生殖系统和肝肠血吸虫病的病原体。这两种血吸虫的基因组、转录组和蛋白质组数据集的可用性现在为在分子水平上探索它们的生物学、宿主相互作用和血吸虫病提供了前所未有的机会。在血吸虫和其他寄生虫的一系列生物学和发育过程中涉及的一类特别重要的分子是G蛋白偶联受体(GPCR)。虽然已经对血吸虫中的GPCR进行了研究,但尚未对密切相关物种之间的这些受体进行详细比较。在这里,我们使用基因组生物信息学方法,鉴定并表征了埃及血吸虫和曼氏血吸虫(两种密切相关的血吸虫物种)中的关键GPCR。

方法

我们使用基于隐马尔可夫模型(HMM)和支持向量机(SVM)的流程,结合系统发育和转录分析,对埃及血吸虫和曼氏血吸虫的GPCR进行分类和子类划分。

结果

我们鉴定并分类了埃及血吸虫和曼氏血吸虫基因组中编码的A、B、C和F类以及一组未分类的GPCR。此外,我们表征了A类(视紫红质样)内的配体特异性亚类(即胺、肽、视蛋白和孤儿)。

结论

除了一个特定进化枝(命名为SmGPR)的成员外,大多数GPCR具有高度的相似性和保守性,该进化枝在埃及血吸虫和曼氏血吸虫之间似乎已经分化,这可能在一定程度上解释了这两种血吸虫之间的一些潜在生物学差异。目前注释的GPCR集为未来细胞GPCR介导的信号转导的功能基因组研究提供了基础,并为未来血吸虫病药物发现工作提供了资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ec0/4100253/47838e52bc85/1756-3305-7-242-1.jpg

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