Evolution of exon 1 of the dopamine D4 receptor (DRD4) gene in primates

The dopamine D4 receptor (DRD4) gene exhibits a large amount of expressed p olymorphism in humans. To understand the evolutionary history of the first exon of DRD4-which in humans contains a polymorphic 12bp tandem duplication , a polymorphic 13bp deletion, and other rare variants-we examined the homo logous exon in thirteen other primate species. The great apes possess a var iable number of tandem repeats in the same region as humans, both within an d among species. In this sense, the 12bp tandem repeat of exon 1 is similar to the 48bp VNTR of exon 3 of DRD4, previously shown to be polymorphic in all primate species examined. The Old World monkeys show no variation in le ngth, and a much higher conservation of amino acid sequence than great apes and humans. The New World monkeys show interspecific differences in length in the region of the 12bp polymorphism, but otherwise show the higher cons ervation seen in Old World monkeys. The different patterns of variation in monkeys compared to apes suggest strong purifying selective pressure on the exon in these monkeys, and somewhat different selection, possibly relaxed selection, in the apes. (C) 2000 Wiley-Liss, Inc.