PT - JOURNAL ARTICLE AU - Philipp Bauknecht AU - Gáspár Jékely TI - Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians AID - 10.1101/063743 DP - 2016 Jan 01 TA - bioRxiv PG - 063743 4099 - http://biorxiv.org/content/early/2016/07/13/063743.short 4100 - http://biorxiv.org/content/early/2016/07/13/063743.full AB - Norepinephrine/noradrenaline is a neurotransmitter implicated in arousal and other aspects of vertebrate behavior and physiology. In invertebrates, adrenergic signaling is considered absent and analogous functions are attributed to the biogenic amine octopamine. Here we describe the coexistence of signaling by norepinephrine, octopamine, and its precursor tyramine in representatives of the two major clades of Bilateria, the protostomes and the deuterostomes. Using phylogenetic analysis and receptor pharmacology we show that six receptors coexisted in the protostome-deuterostome last common ancestor, two each for the three ligands. All receptors were retained in the genomes of the deuterostome Saccoglossus kowalewskii (a hemichordate) and the protostomes Platynereis dumerilii (an annelid) and Priapulus caudatus (a priapulid). Adrenergic receptors were lost from most insects and nematodes and tyramine and octopamine receptors were lost from most deuterostomes. These results clarify the history of monoamine signaling in animals and highlight the importance of studying slowly evolving marine taxa.