Evolution of Dopamine Receptor Genes of the D(1) Class in Vertebrates

The receptors of the dopamine neurotransmitter belong to two unrelated classes named D(1) and D(2). For the D(1) receptor class, only two subtypes are found in mammals, the D(1A) and D(1B,) receptors, whereas additional subtypes, named D(1C), D(1D), and D(1X), have been found in other vertebrate species. Here, we analyzed molecular phylogeny, gene synteny, and gene expression pattern of the D(1) receptor subtypes in a large range of vertebrate species, which leads us to propose a new view of the evolution of D(1) dopamine receptor genes. First, we show that D(1)(C) and D(1)(D) receptor sequences are encoded by orthologous genes. Second, the previously identified Cypriniform D(1)(X) sequence is a teleost-specific paralog of the D(1)(B) sequences found in all groups of jawed vertebrates. Third, zebrafish and several sauropsid species possess an additional D(1)-like gene, which is likely to form another orthology group of vertebrate ancestral genes, which we propose to name D(1)(E). Ancestral jawed vertebrates are thus likely to have possessed four classes of D(1) receptor genes—D(1)(A), D(1)(B(X)), D(1)(C(D)), and D(1)(E)—which arose from large-scale gene duplications. The D(1)(C) receptor gene would have been secondarily lost in the mammalian lineage, whereas the D(1)(E) receptor gene would have been lost independently in several lineages of modern vertebrates. The D(1)(A) receptors are well conserved throughout jawed vertebrates, whereas sauropsid D(1)(C) receptors have rapidly diverged, to the point that they were misidentified as D(1)(D). The functional significance of the D(1)(C) receptor loss is not known. It is possible that the function may have been substituted with D(1)(A) or D(1)(B) receptors in mammals, following the disappearance of D(1)(C) receptors in these species.