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人类和秀丽隐杆线虫 G 蛋白偶联受体的跨基因组聚类。

Cross-Genome Clustering of Human and C. elegans G-Protein Coupled Receptors.

机构信息

National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bangalore 560065, India.

出版信息

Evol Bioinform Online. 2012;8:229-59. doi: 10.4137/EBO.S9405. Epub 2012 Jun 19.

Abstract

G-protein coupled receptors (GPCRs) are one of the largest groups of membrane proteins and are popular drug targets. The work reported here attempts to perform cross-genome phylogeny on GPCRs from two widely different taxa, human versus C. elegans genomes and to address the issues on evolutionary plasticity, to identify functionally related genes, orthologous relationship, and ligand binding properties through effective bioinformatic approaches. Through RPS blast around 1106 nematode GPCRs were given chance to associate with previously established 8 types of human GPCR profiles at varying E-value thresholds and resulted 32 clusters were illustrating co-clustering and class-specific retainsionship. In the significant thresholds, 81% of the C. elegans GPCRs were associated with 32 clusters and 27 C. elegans GPCRs (2%) inferred for orthology. 177 hypothetical proteins were observed in cluster association and could be reliably associated with one of 32 clusters. Several nematode-specific GPCR clades were observed suggesting lineage-specific functional recruitment in response to environment.

摘要

G 蛋白偶联受体(GPCRs)是最大的膜蛋白家族之一,也是热门的药物靶点。本研究旨在对来自两个截然不同的分类群(人类和秀丽隐杆线虫基因组)的 GPCR 进行跨基因组系统发育分析,并通过有效的生物信息学方法解决进化可塑性、识别功能相关基因、同源关系和配体结合特性等问题。通过 RPS blast,约 1106 个线虫 GPCR 有机会与之前建立的 8 种人类 GPCR 图谱在不同的 E 值阈值下相关联,产生了 32 个聚类,显示了共聚类和特定类别的保留关系。在显著的阈值下,81%的秀丽隐杆线虫 GPCR 与 32 个聚类相关,27 个秀丽隐杆线虫 GPCR(2%)被推断为同源。在聚类关联中观察到 177 个假设蛋白,它们可以与 32 个聚类中的一个可靠地相关联。观察到几个线虫特异性 GPCR 分支,表明在应对环境时存在谱系特异性的功能募集。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a649/3396462/e9dbd64130d8/ebo-8-2012-229f1.jpg

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