title: The molecular evolution of G protein-coupled receptors: focus on 5-hydroxytryptamine receptors.
abstract: Phylogenetic comparisons between homologous proteins can provide information on the rates of molecular evolution of the proteins. G protein-coupled receptors are a "superfamily" of proteins which exist in species ranging from yeast to man. Based on an analysis of the percentage of amino acid homology between various species, the rate of molecular evolution of G protein-coupled receptors can be estimated at approx 1% per 10 million years. Based on this assumption, the primordial 5-HT receptor must have evolved more than 700-800 million years ago since the 3 major classes of G protein-coupled 5-HT receptors (i.e. 5-HT1, 5-HT2 and 5-HT6 receptors) are less than 25% homologous. 5-HT5, 5-HT7, 5-HTsnail, 5-HTdro and 5-HT1A receptors differentiated approx 600-700 million years ago, the time period during which vertebrates diverged from invertebrates. The mammalian 5-HT receptor subtypes have differentiated over the past 90 million years. Thus, although a recent flurry of "new" 5-HT receptors have appeared in the literature, the first "primordial" 5-HT receptor evolved over 750 million years ago, a date which likely predates the evolution of muscarinic, dopaminergic and adrenergic receptor systems. This analysis also predicts that a significant number of both mammalian and invertebrate G protein-coupled 5-HT receptor subtypes remain to be identified.
authors.affiliation: Palo Alto Institute for Molecular Medicine, Hillsborough, CA 94010.
authors.forename: S J
authors.initials: SJ
authors.lastname: Peroutka
authors.forename: T A
authors.initials: TA
authors.lastname: Howell
mesh_terms: D000818:Animals; D005075:Biological Evolution; D001717:Birds / Q000378:metabolism; D006224:Cricetinae; D004285:Dogs; D004330:Drosophila; D005658:Fungi / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007313:Insecta / Q000378:metabolism; D051379:Mice; D008967:Molecular Biology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012908:Snails; D013045:Species Specificity; D015003:Yeasts / Q000378:metabolism
chemical_list: D011985:Receptors, Serotonin; D019204:GTP-Binding Proteins