title: Identification and characterization of tandem repeats in exon III of dopamine receptor D4 (DRD4) genes from different mammalian species.
abstract: In this study we have identified and characterized dopamine receptor D4 (DRD4) exon III tandem repeats in 33 public available nucleotide sequences from different mammalian species. We found that the tandem repeat in canids could be described in a novel and simple way, namely, as a structure composed of 15- and 12- bp modules. Tandem repeats composed of 18-bp modules were found in sequences from the horse, zebra, onager, and donkey, Asiatic bear, polar bear, common raccoon, dolphin, harbor porpoise, and domestic cat. Several of these sequences have been analyzed previously without a tandem repeat being found. In the domestic cow and gray seal we identified tandem repeats composed of 36-bp modules, each consisting of two closely related 18-bp basic units. A tandem repeat consisting of 9-bp modules was identified in sequences from mink and ferret. In the European otter we detected an 18-bp tandem repeat, while a tandem repeat consisting of 27-bp modules was identified in a sequence from European badger. Both these tandem repeats were composed of 9-bp basic units, which were closely related with the 9-bp repeat modules identified in the mink and ferret. Tandem repeats could not be identified in sequences from rodents. All tandem repeats possessed a high GC content with a strong bias for C. On phylogenetic analysis of the tandem repeats evolutionary related species were clustered into the same groups. The degree of conservation of the tandem repeats varied significantly between species. The deduced amino acid sequences of most of the tandem repeats exhibited a high propensity for disorder. This was also the case with an amino acid sequence of the human DRD4 exon III tandem repeat, which was included in the study for comparative purposes. We identified proline-containing motifs for SH3 and WW domain binding proteins, potential phosphorylation sites, PDZ domain binding motifs, and FHA domain binding motifs in the amino acid sequences of the tandem repeats. The numbers of potential functional sites varied pronouncedly between species. Our observations provide a platform for future studies of the architecture and evolution of the DRD4 exon III tandem repeat, and they suggest that differences in the structure of this tandem repeat contribute to specialization and generation of diversity in receptor function.
authors.affiliation: Research Institute of Biological Psychiatry, H:S Sct. Hans Hospital, Roskilde, Denmark.
authors.forename: Svend Arild
authors.initials: SA
authors.lastname: Larsen
authors.forename: Line
authors.initials: L
authors.lastname: Mogensen
authors.forename: Rune
authors.initials: R
authors.lastname: Dietz
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Baagøe
authors.forename: Mogens
authors.initials: M
authors.lastname: Andersen
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Henrik Berg
authors.initials: HB
authors.lastname: Rasmussen
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001482:Base Composition / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016000:Cluster Analysis; D019295:Computational Biology; D017124:Conserved Sequence / Q000235:genetics; D030541:Databases, Genetic; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D016415:Sequence Alignment; D013045:Species Specificity; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D050638:Receptors, Dopamine D4