Variability of dopamine D4 receptor (DRD4) gene sequence within and among nonhuman primate species.
The dopamine D4 receptor is one of five receptors known to function in mammalian dopaminergic pathways. The DNA sequence of the human dopamine D4 receptor gene (DRD4) has previously been investigated in several populations and found to be highly polymorphic at both the DNA and amino acid levels, exhibiting at least 25 alleles. This variation results from differences in the number and DNA sequence of a 48-bp (16-amino acid) repeat unit in the coding region of DRD4. In the present study, DRD4 DNA sequence was examined in at least two individuals from each of five nonhuman primate species. All five species exhibit intraspecies variability, including both single nucleotide substitutions and variation in the number of 48-bp repeat units. No differences were found between the two alleles of one individual from a sixth nonhuman species. Within each species, all of the DRD4 alleles share species-specific features, indicating that while repeat-unit variation is nearly ubiquitous, ancestral variation has been lost and subsequently regenerated in each of the evolutionary lineages studied. Chimpanzees and gorillas share a unique 12-bp deletion in the coding region of DRD4, outside the repeat-unit segment of the gene. This suggest that the extant chimpanzee DRD4 is more closely related to the gorilla DRD4 than either is to the human DRD4.
Search and Development Division, DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0328.
K J
KJ
Livak
J
J
Rogers
J B
JB
Lichter
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon; D014644:Genetic Variation; D006071:Gorilla gorilla / Q000235:genetics; D015186:Hominidae / Q000235:genetics*; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D010215:Papio / Q000235:genetics; D010802:Phylogeny; D011148:Pongo pygmaeus / Q000235:genetics; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D012453:Saimiri / Q000235:genetics*; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D003062:Codon; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4