Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors

<p>Abstract</p> <p>Background</p> <p>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 putati...

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Main Authors: Sowdhamini Ramanathan, Metpally Raghu
Format: Article
Language:English
Published: BMC 2005-08-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/6/106
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spelling doaj-a40cbb9ecff04be4874be6bf184ccf002020-11-25T00:49:00ZengBMCBMC Genomics1471-21642005-08-016110610.1186/1471-2164-6-106Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptorsSowdhamini RamanathanMetpally Raghu<p>Abstract</p> <p>Background</p> <p>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 <it>Drosophila</it> 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.</p> <p>Results</p> <p>Cross-genome phylogenetic analyses were performed to identify eight major groups of GPCRs dividing them into 32 clusters of 371 human and 113 <it>Drosophila</it> proteins (excluding olfactory, taste and gustatory receptors) and reveal unexpected levels of evolutionary conservation across human and <it>Drosophila</it> GPCRs. We also observe that members of human chemokine receptors, involved in immune response, and most of nucleotide-lipid receptors (except opsins) do not have counterparts in <it>Drosophila</it>. Similarly, a group of <it>Drosophila</it> GPCRs (methuselah receptors), associated in aging, is not present in humans.</p> <p>Conclusion</p> <p>Our analysis suggests ligand class association to 52 unknown <it>Drosophila</it> receptors and 95 unknown human GPCRs. A higher level of phylogenetic organization was revealed in which clusters with common domain architecture or cellular localization or ligand structure or chemistry or a shared function are evident across human and <it>Drosophila</it> genomes. Such analyses will prove valuable for identifying the natural ligands of <it>Drosophila</it> and human orphan receptors that can lead to a better understanding of physiological and pathological roles of these receptors.</p> http://www.biomedcentral.com/1471-2164/6/106
collection DOAJ
language English
format Article
sources DOAJ
author Sowdhamini Ramanathan
Metpally Raghu
spellingShingle Sowdhamini Ramanathan
Metpally Raghu
Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors
BMC Genomics
author_facet Sowdhamini Ramanathan
Metpally Raghu
author_sort Sowdhamini Ramanathan
title Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors
title_short Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors
title_full Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors
title_fullStr Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors
title_full_unstemmed Cross genome phylogenetic analysis of human and <it>Drosophila</it> G protein-coupled receptors: application to functional annotation of orphan receptors
title_sort cross genome phylogenetic analysis of human and <it>drosophila</it> g protein-coupled receptors: application to functional annotation of orphan receptors
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2005-08-01
description <p>Abstract</p> <p>Background</p> <p>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 <it>Drosophila</it> 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.</p> <p>Results</p> <p>Cross-genome phylogenetic analyses were performed to identify eight major groups of GPCRs dividing them into 32 clusters of 371 human and 113 <it>Drosophila</it> proteins (excluding olfactory, taste and gustatory receptors) and reveal unexpected levels of evolutionary conservation across human and <it>Drosophila</it> GPCRs. We also observe that members of human chemokine receptors, involved in immune response, and most of nucleotide-lipid receptors (except opsins) do not have counterparts in <it>Drosophila</it>. Similarly, a group of <it>Drosophila</it> GPCRs (methuselah receptors), associated in aging, is not present in humans.</p> <p>Conclusion</p> <p>Our analysis suggests ligand class association to 52 unknown <it>Drosophila</it> receptors and 95 unknown human GPCRs. A higher level of phylogenetic organization was revealed in which clusters with common domain architecture or cellular localization or ligand structure or chemistry or a shared function are evident across human and <it>Drosophila</it> genomes. Such analyses will prove valuable for identifying the natural ligands of <it>Drosophila</it> and human orphan receptors that can lead to a better understanding of physiological and pathological roles of these receptors.</p>
url http://www.biomedcentral.com/1471-2164/6/106
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