Phylogenetic tree analysis of G protein-coupled 5-HT receptors: implications for receptor nomenclature

The nomenclature system used to characterize 5-hydroxytryptamine receptor subtypes remains controversial. To date, the majority of nomenclature systems have been on the differential pharmacological properties of the receptors. However, the availability of molecular biological data allows for a nomenclature system based on the structural properties of the receptors. The evolutionary relationships between the known G protein-coupled 5-HT receptor subtypes were determined by a phylogenetic tree analysis. The data indicate that 2 major classes of G protein-coupled 5-HT receptors have evolved. Each of the 2 branches differentiate into additional 5-HT receptor subtypes. The most recent branching of 5-HT receptor subtypes occurs at the level of individual species. These data also indicate that the degree of structural similarity (e.g. 93% identify between human and rat 5-HT1B receptors) does not necessarily correlate with pharmacological similarity. Phylogenetic tree analysis allows for a nomenclature framework that can be easily expanded to incorporate additional 5-HT receptor subtypes that have yet to be identified.