The G protein-coupled receptor subset of the rat genome - PubMed (original) (raw)

Comparative Study

The G protein-coupled receptor subset of the rat genome

David E Gloriam et al. BMC Genomics. 2007.

Abstract

Background: The superfamily of G protein-coupled receptors (GPCRs) is one of the largest within most mammals. GPCRs are important targets for pharmaceuticals and the rat is one of the most widely used model organisms in biological research. Accurate comparisons of protein families in rat, mice and human are thus important for interpretation of many physiological and pharmacological studies. However, current automated protein predictions and annotations are limited and error prone.

Results: We searched the rat genome for GPCRs and obtained 1867 full-length genes and 739 pseudogenes. We identified 1277 new full-length rat GPCRs, whereof 1235 belong to the large group of olfactory receptors. Moreover, we updated the datasets of GPCRs from the human and mouse genomes with 1 and 43 new genes, respectively. The total numbers of full-length genes (and pseudogenes) identified were 799 (583) for human and 1783 (702) for mouse. The rat, human and mouse GPCRs were classified into 7 families named the Glutamate, Rhodopsin, Adhesion, Frizzled, Secretin, Taste2 and Vomeronasal1 families. We performed comprehensive phylogenetic analyses of these families and provide detailed information about orthologues and species-specific receptors. We found that 65 human Rhodopsin family GPCRs are orphans and 56 of these have an orthologue in rat.

Conclusion: Interestingly, we found that the proportion of one-to-one GPCR orthologues was only 58% between rats and humans and only 70% between the rat and mouse, which is much lower than stated for the entire set of all genes. This is in mainly related to the sensory GPCRs. The average protein sequence identities of the GPCR orthologue pairs is also lower than for the whole genomes. We found these to be 80% for the rat and human pairs and 90% for the rat and mouse pairs. However, the proportions of orthologous and species-specific genes vary significantly between the different GPCR families. The largest diversification is seen for GPCRs that respond to exogenous stimuli indicating that the variation in their repertoires reflects to a large extent the adaptation of the species to their environment. This report provides the first overall roadmap of the GPCR repertoire in rat and detailed comparisons with the mouse and human repertoires.

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Figures

Figure 1

Phylogenetic analysis of the Rhodopsin family. The figure shows a phylogenetic tree of Rhodopsin family receptors. Rhodopsins which display ambiguous relationships were analysed in separate (see Figure 2). Species-specific receptors have names in bold style. The ligand types of the receptors are indicated with the following colours; red: orphan, blue: peptide, lilac: amine, green: lipid-like, brown: purine, turquoise: opsin and black: other. The first pie chart above the trees shows the proportions of human-rat one-to-one orthologues (O), human specific (H) and rat specific (R) members. The second pie chart displays the proportions of rat-mouse one-to-one orthologues (O), rat specific (R) and mouse specific (M) members. This phylogenetic tree is a consensus tree of 2 consensus trees derived from 100 maximum parsimony and neighbour joining analyses, respectively, and calculated using the UNIX version of the Phylip 3.6 package [73].

Figure 2

Rhodopsin family receptors with ambiguous relationships to other members. Groups, pairs and "single" Rhodopsin family receptors that display ambiguous relationships to other members (see material and methods). These are shown in order of decreasing sequence identity (given in the lower right corner of each box). Species-specific receptors have names in bold style. The ligand types of the receptors are indicated with the following colours; red: orphan, blue: peptide, lilac: amine, green: lipid-like, brown: purine, turquoise: opsin and black: other. The phylogenetic trees are consensus trees of 100 maximum likelihood trees for which branch lengths were calculated using TreePuzzle (see material and method). The olfactory subfamily/group of the Rhodopsin family was analysed in a separate phylogenetic analysis [see Additional files 7 and 8].

Figure 3

Phylogenetic trees of the Glutamate, Adhesion, Frizzled, Secretin and Taste2 families. The figure shows the consensus trees of 100 maximum parsimony trees of the human and rat a) Glutamate, b) Adhesion, c) Frizzled, d) Secretin and e) Taste2 (mouse included) GPCR families. The first pie chart after the each family name shows the proportions of human-rat one-to-one orthologues (O), human specific (H) and rat specific (R) members. The second pie chart displays the proportions of rat-mouse one-to-one orthologues (O), rat specific (R) and mouse specific (M) members. In Figure 3, the place of the large group of V2Rs is indicated with an arrow. Rat sequences that were excluded from the phylogenetic analysis because they were incomplete (due to gaps in the genome assembly) are displayed with dashed branches.

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The G protein-coupled receptor subset of the rat genome - PubMed (original) (raw)