Evolution of the α₂-adrenoreceptors in vertebrates: ADRA2D is absent in mammals and crocodiles

Evolutionary studies of genes that have been functionally characterized and whose variation has been associated with pathological conditions represent an opportunity to understand the genetic basis of pathologies. α₂-Adrenoreceptors (ADRA2) are a class of G protein-coupled receptors that regulate several physiological processes including blood pressure, platelet aggregation, insulin secretion, lipolysis, and neurotransmitter release. This gene family has been extensively studied from a molecular/physiological perspective, yet much less is known about its evolutionary history. Accordingly, the goal of this study was to investigate the evolutionary history of α₂-adrenoreceptors (ADRA2) in vertebrates. Our results show that in addition to the three well-recognized α₂-adrenoreceptor genes (ADRA2A, ADRA2B and ADRA2C), we recovered a clade that corresponds to the fourth member of the α₂-adrenoreceptor gene family (ADRA2D). We also recovered a clade that possesses two ADRA2 sequences found in two lamprey species. Furthermore, our results show that mammals and crocodiles are characterized by possessing three α₂-adrenoreceptor genes, whereas all other vertebrate groups possess the full repertoire of α₂-adrenoreceptor genes. Among vertebrates ADRA2D seems to be a dispensable gene, as it was lost two independent times during the evolutionary history of the group. Additionally, we found that most examined species possess the most common alleles described for humans; however, there are cases in which non-human mammals possess the alternative variant. Finally, transcript abundance profiles revealed that during the early evolutionary history of gnathostomes, the expression of ADRA2D in different taxonomic groups became specialized to different tissues, but in the ancestor of sarcopterygians this specialization would have been lost.