Human D4 dopamine receptor (D4DR) is polymorphic in terms of the repea
t numbers of the 48-base pairs (bp) sequence located in the third cyto
plasmic loop of the receptor. The repeated sequence and its polymorphi
sm in D4DR genes have also been identified in higher non-human primate
s, suggesting that the structure of D4DR has been maintained during pr
imate evolution. To clarify the origin and divergence of the polymorph
ism in the D4DR gene, we determined the nucleotide sequence of this re
gion of the D4DR gene in several species of prosimians and the tree sh
rew, a species which is closely related to primates. Prosimians except
the tarsier had one or two unit(s) of the 48-bp sequence, and conserv
ed sequences were recognized in most of the units of the prosimians. T
he tree shrew had only one unit of the 48-bp sequence, and its sequenc
e was 71-75% identical to those of the units of galago, loris, and lem
ur. These findings suggest that the ancestral primate presumably had o
ne 48-bp unit, and duplication of the unit occurred at the stage of pr
osimians. Tarsiers appeared to be distinct from other prosimians and s
imians because of the high repeat numbers of units and their sequences
.