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First published on February 1, 2005; DOI: 10.1124/mol.104.009001


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Received for publication November 15, 2004.
Revised February 1, 2005.
Accepted for publication February 1, 2005.

The repertoire of G-protein coupled receptors in fully sequenced genomes

Robert Fredriksson 1 Helgi B. Schioth 1*

1 Uppsala University

* Address correspondence to: E-mail: helgis{at}bmc.uu.se

Abstract

The super family of G-protein coupled receptors (GPCRs) is one of the largest and most studied families of proteins. We created Hidden Markov Models based on sorted groups of GPCRs from our previous detailed phylogenetic classification of human GPCRs and added several other models based on receptors not found in mammals. We used these models to search entire Genscan datasets from 13 species whose genomes are nearly completely sequenced. We found over 5000 unique GPCRs that were divided into 15 main groups, while the largest one, the Rhodopsin family, was subdivided into 13 subclasses. The results show that the main families in the human genome; Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin arose prior the split of nematodes from the chordate lineage. Moreover, several of the subgroups of the Rhodopsin family arose prior to the split of the linage leading to vertebrates. We also searched EST databases and identified over 20 000 sequences that match GPCRs. While the GPCRs represent typically 1-2% of the Genscan predictions, the ESTs that match GPCRs are typically only 0.01-0.001%, indicating that GPCRs in most of the groups are expressed at low levels. We also provide searchable datasets that may be used for annotation and further detailed analysis of the GPCR family. This study provides an extensive overview of the expansion of the gene repertoire for families and subgroups of GPCRs.


Key words: Comparative genome analyses, Pharmacogenomic analyses


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