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Cross genome phylogenetic analysis of human and Drosophila G protein-coupled receptors application to functional annotation of orphan receptors.doc

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Cross genome phylogenetic analysis of human and Drosophila G protein-coupled receptors application to functional annotation of orphan receptors

BMC Genomics BioMedCentral Research article Open Access Cross genome phylogenetic analysis of human and Drosophila G protein-coupled receptors: application to functional annotation of orphan receptors Raghu Prasad Rao Metpally and Ramanathan Sowdhamini* Address: National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bellary Road, Bangalore 560065, INDIA Email: Raghu Prasad Rao Metpally - raghu@ncbs.res.in; Ramanathan Sowdhamini* - mini@ncbs.res.in * Corresponding author Published: 10 August 2005 Received: 21 March 2005 Accepted: 10 August 2005 BMC Genomics 2005, 6:106 doi:10.1186/1471-2164-6-106 This article is available from: /1471-2164/6/106 ? 2005 Metpally and Sowdhamini; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The cell-membrane G-protein coupled receptors (GPCRs) are one of the largest known superfamilies and are the main focus of intense pharmaceutical research due to their key role in cell physiology and disease. A large number of putative GPCRs are orphans with no identified natural ligands. The first step in understanding the function of orphan GPCRs is to identify their ligands. Phylogenetic clustering methods were used to elucidate the chemical nature of receptor ligands, which led to the identification of natural ligands for many orphan receptors. We have clustered human and Drosophila receptors with known ligands and orphans through cross genome phylogenetic analysis and hypothesized higher relationship of co-clustered members that would ease ligand identification, as related receptors share ligands with similar structure or class. Results: Cross-genome phylogenetic analyses were performed to