Elsevier

Genomics

Volume 88, Issue 3, September 2006, Pages 263-273
Genomics

Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse

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Abstract

Understanding differences in the repertoire of orthologous gene pairs is vital for interpretation of pharmacological and physiological experiments if conclusions are conveyed between species. Here we present a comprehensive dataset for G protein-coupled receptors (GPCRs) in both human and mouse with a phylogenetic road map. We performed systematic searches applying several search tools such as BLAST, BLAT, and Hidden Markov models and searches in literature data. We aimed to gather a full-length version of each human or mouse GPCR in only one copy referring to a single chromosomal position. Moreover, we performed detailed phylogenetic analysis of the transmembrane regions of the receptors to establish accurate orthologous pairs. The results show the identity of 495 mouse and 400 human functional nonolfactory GPCRs. Overall, 329 of the receptors are found in one-to-one orthologous pairs, while 119 mouse and 31 human receptors originate from species-specific expansions or deletions. The average percentage similarity of the orthologue pairs is 85%, while it varies between the main GRAFS families from an average of 59 to 94%. The orthologous pairs for the lipid-binding GPCRs had the lowest levels of conservation, while the biogenic amines had highest levels of conservation. Moreover, we searched for expressed sequence tags (ESTs) and identified more than 17,000 ESTs matching GPCRs in mouse and human, providing information about their expression patterns. On the whole, this is the most comprehensive study of the gene repertoire that codes for human and mouse GPCRs. The datasets are available for downloading.

Keywords

GPCR
Glutamate
Rhodopsin
Adhesion
Frizzled
Taste2
Secretin

Abbreviations

BLAST
basic local alignment search tool
BLAT
BLAST-like alignment tool
EST
expressed sequence tag
GPCR
G protein-coupled receptor
HMM
Hidden Markov model
MP
maximum parsimony
RPS-BLAST
reverse positions-specific BLAST
TM
transmembrane region
7TM
seven transmembrane regions

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