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.

Non-thalamic origin of zebrafish sensory relay nucleus: convergent evolution of visual pathways in amniotes and teleosts

“…In addition to the variation in neuronal connectivity that we reveal here, we have already demonstrated unexpected diversity of dopamine systems, despite their involvement in similar physiological/behavioral properties across vertebrate groups Yamamoto et al, 2015.…”

Functional Characterisation of Eel Dopamine D2 Receptors and Involvement in the Direct Inhibition of Pituitary Gonadotrophins

“…The presence of two D2‐R paralogues in the eel probably results from the teleost specific whole genome duplication (3R) . Teleosts are known to possess more DA receptor genes compared to tetrapods . In the goldfish, three D2‐R genes were reported , although phylogenetical analysis suggests that the additional one, compared to the eel, may result from the specific tetraploidisation of this group .…”

“…In zebrafish, three D2‐R genes were also isolated and initially named D2a, D2b and D2c , a nomenclature that we used in a previous study . However, they were renamed D2a, D2like and D2b, respectively, by Ensembl/ZFIN . Recent phylogenetical studies further showed that the zebrafish D2a and D2b are 3R‐duplicated genes, orthologous to the amniote D 2 , whereas the D2like would be an additional gene lost in tetrapods (renamed D8) .…”

Song in an Affiliative Context Relates to the Neural Expression of Dopamine- and Neurotensin-Related Genes in Male European Starlings

“…All sequences match the specified targets using NCBI BLAST. The D1 receptor primer specifically targets the D1 A receptor subtype [Yamamoto et al, 2015], which is highly expressed in Area X and septum of zebra finches [Kubikova et al, 2010]; the D2 receptor primer targets the D2 receptor subtype of the D2 family (which also includes D3 and D4 receptors) [Yamamoto et al, 2015], which is expressed in VTA, Area X, and septum [Kubikova et al, 2010]. …”