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Comparative Study
. 2003 Apr 15;100(8):4903-8.
doi: 10.1073/pnas.0230374100. Epub 2003 Apr 4.

The G protein-coupled receptor repertoires of human and mouse

Demetrios K Vassilatis  1 , John G Hohmann, Hongkui Zeng, Fusheng Li, Jane E Ranchalis, Marty T Mortrud, Analisa Brown, Stephanie S Rodriguez, John R Weller, Abbie C Wright, John E Bergmann, George A Gaitanaris
Affiliations
Comparative Study

The G protein-coupled receptor repertoires of human and mouse

Demetrios K Vassilatis et al. Proc Natl Acad Sci U S A. .

Abstract

Diverse members of the G protein-coupled receptor (GPCR) superfamily participate in a variety of physiological functions and are major _targets of pharmaceutical drugs. Here we report that the repertoire of GPCRs for endogenous ligands consists of 367 receptors in humans and 392 in mice. Included here are 26 human and 83 mouse GPCRs not previously identified. A direct comparison of GPCRs in the two species reveals an unexpected level of orthology. The evolutionary preservation of these molecules argues against functional redundancy among highly related receptors. Phylogenetic analyses cluster 60% of GPCRs according to ligand preference, allowing prediction of ligand types for dozens of orphan receptors. Expression profiling of 100 GPCRs demonstrates that most are expressed in multiple tissues and that individual tissues express multiple GPCRs. Over 90% of GPCRs are expressed in the brain. Strikingly, however, the profiles of most GPCRs are unique, yielding thousands of tissue- and cell-specific receptor combinations for the modulation of physiological processes.

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Figures

Figure 1
Figure 1
Phylogenetic trees of human endoGPCRs. Lines corresponding to individual proteins are colored black for those with known ligands, red for orphan proteins, and blue for proteins with seven transmembrane domains but no homology to known endoGPCRs. The Class A tree was split in two parts due to size considerations (arrow line indicates the connection). Clusters of endoGPCRs with significant predictive value as to ligands are highlighted in blue on these bootstrap consensus trees (bootstrap values not shown). The ruler at the bottom of each tree indicates the horizontal distance equal to 10% sequence divergence.
Figure 2
Figure 2
Expression profiles of nine endoGPCRs by RT-PCR.
Figure 3
Figure 3
Summary of tissue expression of 100 endoGPCR genes. Genes were analyzed individually by RT-PCR as shown and the intensity of the observed bands determined by scanning. Each gene is represented by a single row of colored boxes, with four different expression levels: no expression, blue; low expression, purple; moderate expression, dark red; strong expression, pure red. Gene and tissues, as well as groups of expression patterns, are indicated.
Figure 4
Figure 4
Representative in situ hybridization photomicrographs of endoGPCR expression in the mouse brain. (a) GPR63 in the Ammons horn (CA) regions of the hippocampus; (b) PGR7 in the habenula; (c) GRCA in the cortex and thalamus; (d) GPR63 in the Purkinje cells of the cerebellum; (e) GPR37 in the frontal cortex; (f) GPR26 in the inferior olive; (g) GPR50 in the cells lining the third ventricle; and (h) PGR15 in the preoptic region of the hypothalamus. Vertical lines on sagittal mouse brain drawing represent approximate coronal plane of photomicrographs. (Bars = 500 μm.)
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