Classification of Dopamine Receptor Genes in Vertebrates: Nine Subtypes in Osteichthyes

Abstract

Dopamine neurotransmission regulates various brain functions, and its regulatory roles are mediated by two families of G protein-coupled receptors: the D₁ and D₂ receptor families. In mammals, the D₁ family comprises two receptor subtypes (D₁ and D₅), while the D₂ family comprises three receptor subtypes (D₂, D₃ and D₄). Phylogenetic analyses of dopamine receptor genes strongly suggest that the common ancestor of Osteichthyes (bony jawed vertebrates) possessed four subtypes in the D₁ family and five subtypes in the D₂ family. Mammals have secondarily lost almost half of the ancestral dopamine receptor genes, whereas nonmammalian species kept many of them. Although the mammalian situation is an exception among Osteichthyes, the current classification and characterization of dopamine receptors are based on mammalian features, which have led to confusion in the identification of dopamine receptor subtypes in nonmammalian species. Here we begin by reviewing the history of the discovery of dopamine receptors in vertebrates. The recent genome sequencing of coelacanth, gar and elephant shark led to the proposal of a refined scenario of evolution of dopamine receptor genes. We also discuss a current problem of nomenclature of dopamine receptors. Following the official nomenclature of mammalian dopamine receptors from D₁ to D₅, we propose to name newly identified receptor subtypes from D₆ to D₉ in order to facilitate the use of an identical name for orthologous genes among different species. To promote a nomenclature change which allows distinguishing the two dopamine receptor families, a nomenclature consortium is needed. This comparative perspective is crucial to correctly interpret data obtained in animal studies on dopamine-related brain disorders, and more fundamentally, to understand the characteristics of dopamine neurotransmission in vertebrates.