VARIABILITY OF DOPAMINE D-4 RECEPTOR (DRD4) GENE SEQUENCE WITHIN AND AMONG NONHUMAN PRIMATE SPECIES

The dopamine D-4 receptor is one of five receptors known to function i n mammalian dopaminergic pathways. The DNA sequence of the human dopam ine D-4 receptor gene (DRD4) has previously been investigated in sever al populations and found to be highly polymorphic at both the DNA and amino acid levels, exhibiting at least 25 alleles. This variation resu lts from differences in the number and DNA sequence of a 48-bp (16 ami no acid) repeat unit in the coding region of DRD4. In the present stud y, DRD4 DNA sequence was examined in at least two individuals from eac h of five nonhuman primate species. All five species exhibit intraspec ies variability, including both single nucleotide substitutions and va riation in the number of 48-bp repeat units. No differences were found between the two alleles of one individual from a sixth nonhuman speci es. Within each species, all of the DRD4 alleles share species-specifi c features, indicating that while repeat-unit variation is nearly ubiq uitous, ancestral variation has been lost and subsequently regenerated in each of the evolutionary lineages studied. Chimpanzees and gorilla s share a unique 12-bp deletion in the coding region of DRD4, outside the repeat-unit segment of the gene. This suggests that the extant chi mpanzee DRD4 is more closely related to the gorilla DRD4 than either i s to the human DRD4.