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The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents.

Haitina T, Fredriksson R, Foord SM, Schiöth HB, Gloriam DE - BMC Genomics (2009)

Bottom Line: We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire.Several GPCR gene expansions characteristic for rodents are not found in dog.The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. tatjana.haitina@neuro.uu.se

ABSTRACT

Background: The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species.

Results: We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog.

Conclusion: The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

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Consensus trees of the human (hs) and dog (cf) Adhesion, Frizzled, Glutamate and Secretin GPCR families. Each tree is based on 100 Maximum Parsimony trees. The sequence alignments used for phylogenetic calculations were based on the transmembrane segments. For each GPCR family a pie-chart displays the average pairwise percentages of protein sequence identity between human, mouse and dog one-to-one orthologs.
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Figure 2: Consensus trees of the human (hs) and dog (cf) Adhesion, Frizzled, Glutamate and Secretin GPCR families. Each tree is based on 100 Maximum Parsimony trees. The sequence alignments used for phylogenetic calculations were based on the transmembrane segments. For each GPCR family a pie-chart displays the average pairwise percentages of protein sequence identity between human, mouse and dog one-to-one orthologs.

Mentions: We performed phylogenetic analyses of all dog and human GRAFS GPCR protein sequences and identified orthologs and species-specific genes. The latter represent paralogous genes that have arisen or been lost specifically in either human or dog or the lineages leading to them. Consensus trees of 100 Maximum Parsimony phylogenetic trees and the average amino acid sequences identities of receptor orthologs are presented in Figure 1: Rhodopsin family and Figure 2:Glutamate, Adhesion, Frizzled and Secretin families. Dog genes missing in human are listed in Table 2, whereas human GPCR genes not found in the dog and/or rodent genomes are listed in Table 3.


The G protein-coupled receptor subset of the dog genome is more similar to that in humans than rodents.

Haitina T, Fredriksson R, Foord SM, Schiöth HB, Gloriam DE - BMC Genomics (2009)

Consensus trees of the human (hs) and dog (cf) Adhesion, Frizzled, Glutamate and Secretin GPCR families. Each tree is based on 100 Maximum Parsimony trees. The sequence alignments used for phylogenetic calculations were based on the transmembrane segments. For each GPCR family a pie-chart displays the average pairwise percentages of protein sequence identity between human, mouse and dog one-to-one orthologs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651185&req=5

Figure 2: Consensus trees of the human (hs) and dog (cf) Adhesion, Frizzled, Glutamate and Secretin GPCR families. Each tree is based on 100 Maximum Parsimony trees. The sequence alignments used for phylogenetic calculations were based on the transmembrane segments. For each GPCR family a pie-chart displays the average pairwise percentages of protein sequence identity between human, mouse and dog one-to-one orthologs.
Mentions: We performed phylogenetic analyses of all dog and human GRAFS GPCR protein sequences and identified orthologs and species-specific genes. The latter represent paralogous genes that have arisen or been lost specifically in either human or dog or the lineages leading to them. Consensus trees of 100 Maximum Parsimony phylogenetic trees and the average amino acid sequences identities of receptor orthologs are presented in Figure 1: Rhodopsin family and Figure 2:Glutamate, Adhesion, Frizzled and Secretin families. Dog genes missing in human are listed in Table 2, whereas human GPCR genes not found in the dog and/or rodent genomes are listed in Table 3.

Bottom Line: We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire.Several GPCR gene expansions characteristic for rodents are not found in dog.The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. tatjana.haitina@neuro.uu.se

ABSTRACT

Background: The dog is an important model organism and it is considered to be closer to humans than rodents regarding metabolism and responses to drugs. The close relationship between humans and dogs over many centuries has lead to the diversity of the canine species, important genetic discoveries and an appreciation of the effects of old age in another species. The superfamily of G protein-coupled receptors (GPCRs) is one of the largest gene families in most mammals and the most exploited in terms of drug discovery. An accurate comparison of the GPCR repertoires in dog and human is valuable for the prediction of functional similarities and differences between the species.

Results: We searched the dog genome for non-olfactory GPCRs and obtained 353 full-length GPCR gene sequences, 18 incomplete sequences and 13 pseudogenes. We established relationships between human, dog, rat and mouse GPCRs resolving orthologous pairs and species-specific duplicates. We found that 12 dog GPCR genes are missing in humans while 24 human GPCR genes are not part of the dog GPCR repertoire. There is a higher number of orthologous pairs between dog and human that are conserved as compared with either mouse or rat. In almost all cases the differences observed between the dog and human genomes coincide with other variations in the rodent species. Several GPCR gene expansions characteristic for rodents are not found in dog.

Conclusion: The repertoire of dog non-olfactory GPCRs is more similar to the repertoire in humans as compared with the one in rodents. The comparison of the dog, human and rodent repertoires revealed several examples of species-specific gene duplications and deletions. This information is useful in the selection of model organisms for pharmacological experiments.

Show MeSH
Related in: MedlinePlus