Timing of the Functional Diversification of α- and β-Adrenoceptors in Fish and Other Vertebrates

Adrenoceptors (ARs) are G protein-coupled receptors found throughout the vertebrates. Their pharmacology and preliminary phylogenetic analyses suggest that ARs are classified as alpha(1), alpha(2) (and their subtypes), and beta(1), beta(2), and beta(3). However, the relationships among subtypes of this superfamily, as well as both the pattern and the timing of their diversification, are poorly understood. In addition, fish AR subtypes possess pharmacologies and tissue distributions that only partially overlap with those of their mammalian counterparts, in spite of their apparent orthologous relationships within subtypes. Here we analyze 136 sequences in a range of vertebrates, including fish, to resolve these issues. We show that diversification of ARs occurred during duplication events that occurred within distinct time periods. Each period maps to whole-genome duplication events, two in vertebrates and one in fish. We also show that ARs underwent multiple duplications within these broad windows and that fish ARs underwent extensive gene loss after duplications that promoted their functional divergence with respect to other vertebrates.