title: Evolutionary origin of cholinergic macromolecules and thyroglobulin.
abstract: We have compared the amino acid sequences of proteins that are involved in acetylcholine (AcCho) metabolism and cholinergic neurotransmission: choline acetyltransferase (ChoAcTase), acetylcholinesterase (AcChoEase), and a neuronal alpha subunit of nicotinic AcCho receptor (AcChoR). A comparison of Drosophila ChoAcTase and rat neuronal alpha subunit of AcChoR shows a limited segmental type homology, which may suggest a similar acetylcholine binding site in the two proteins evolving by convergence. We note a global homology of 21-44% identity between Drosophila ChoAcTase and Torpedo AcChoEase. Six homologous segments of 40-60 amino acids cover 38% and 54% of the sequences, raising the possibility of a common evolutionary origin. We also note that mammalian thyroglobulin (TG), the precursor for thyroid hormones, contains an AcChoEase-like sequence at its carboxyl end. This homology raises the possibility that the gene for TG has evolved by gene fusion or condensation (i.e., recruiting a preexisting redundant copy of a gene for AcChoEase during vertebrate evolution). Our results demonstrate that the record of evolutionary history for nervous system proteins can be read across the boundaries of separation between vertebrates and invertebrates. They also provide molecular evidence for the common evolutionary origins of the nervous and endocrine systems in vertebrates--both evolving to make intercellular communication possible.
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.forename: N
authors.initials: N
authors.lastname: Itoh
authors.forename: P M
authors.initials: PM
authors.lastname: Salvaterra
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002795:Choline O-Acetyltransferase / Q000235:genetics*; D004330:Drosophila / Q000201:enzymology; D046911:Macromolecular Substances; D011978:Receptors, Nicotinic / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013954:Thyroglobulin / Q000235:genetics*; D014101:Torpedo
chemical_list: D046911:Macromolecular Substances; D011978:Receptors, Nicotinic; D013954:Thyroglobulin; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine