CHROMOSOMAL ORGANIZATION OF ADRENERGIC-RECEPTOR GENES

The adrenergic receptors (ARs) (subtypes α1, α2, β1, and β2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. We have previously assigned the genes for β2- and α2-AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, we have now mapped the α1-AR gene to chromosome 5q32→q34, the same position as β2-AR, and the β1-AR gene to chromosome 10q24→q26, the region where α2-AR is located. In mouse, both α2- and β1-AR genes were assigned to chromosome 19, and the α1-AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the α1- and β2-AR genes in humans are within 300 kilobases (kb) and the distance between the α2 and β1-AR genes is <225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediating the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families of receptor molecules.