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The G protein-coupled receptor subset of the rat genome.

Gloriam DE, Fredriksson R, Schiöth HB - BMC Genomics (2007)

Bottom Line: We found that 65 human Rhodopsin family GPCRs are orphans and 56 of these have an orthologue in rat.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. DavidGloriam@googlemail.com

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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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].
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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].

Mentions: We produced phylogenetic trees for each GPCR family. These are shown in Figures 1, 2, 3 and as additional files of this article [see Additional files 5, 6, 7], which all also hold pie charts of the proportions of orthologous and species-specific GPCRs in the three species analysed. The mouse Glutamate, Rhodopsin (non-ORs), Adhesion, Frizzled and Secretin GPCRs are not included in these trees since they have been described before in relation to the human repertoires [21], and the exact orthologous and paralogous relationships are viewed in a table listing the receptors in the three species studied [see Additional File 1]. All receptors sequences were trimmed prior to the phylogenetic analysis to isolate the transmembrane domains which are the regions that are conserved throughout the GPCR families. A special approach was used for the phylogenetic analysis of the Rhodopsin family which is very challenging because of its size and diversity. Some Rhodopsin GPCRs have diverged to the extent that their relationships to the rest of the family members cannot be determined. These receptor sequences do not show stable tree topology and group with different subfamilies when using different phylogenetic algorithms. The ambiguous grouping of these receptors is also illustrated by the fact that when their sequences are searched against the whole dataset using BLAST the best matches (e.g. top 5) to these receptors belong to different subfamilies. We minimised the above problems by separating the receptors with a low sequence identity from the main part of the dataset when performing phylogenetic analyses. This was done by applying iteratively higher thresholds of percentage sequence identity on the dataset until a stable tree topology could be obtained.


The G protein-coupled receptor subset of the rat genome.

Gloriam DE, Fredriksson R, Schiöth HB - BMC Genomics (2007)

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].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2117022&req=5

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].
Mentions: We produced phylogenetic trees for each GPCR family. These are shown in Figures 1, 2, 3 and as additional files of this article [see Additional files 5, 6, 7], which all also hold pie charts of the proportions of orthologous and species-specific GPCRs in the three species analysed. The mouse Glutamate, Rhodopsin (non-ORs), Adhesion, Frizzled and Secretin GPCRs are not included in these trees since they have been described before in relation to the human repertoires [21], and the exact orthologous and paralogous relationships are viewed in a table listing the receptors in the three species studied [see Additional File 1]. All receptors sequences were trimmed prior to the phylogenetic analysis to isolate the transmembrane domains which are the regions that are conserved throughout the GPCR families. A special approach was used for the phylogenetic analysis of the Rhodopsin family which is very challenging because of its size and diversity. Some Rhodopsin GPCRs have diverged to the extent that their relationships to the rest of the family members cannot be determined. These receptor sequences do not show stable tree topology and group with different subfamilies when using different phylogenetic algorithms. The ambiguous grouping of these receptors is also illustrated by the fact that when their sequences are searched against the whole dataset using BLAST the best matches (e.g. top 5) to these receptors belong to different subfamilies. We minimised the above problems by separating the receptors with a low sequence identity from the main part of the dataset when performing phylogenetic analyses. This was done by applying iteratively higher thresholds of percentage sequence identity on the dataset until a stable tree topology could be obtained.

Bottom Line: We found that 65 human Rhodopsin family GPCRs are orphans and 56 of these have an orthologue in rat.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. DavidGloriam@googlemail.com

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.

Show MeSH
Related in: MedlinePlus