title: Natural genomic amplification of cholinesterase genes in animals.
abstract: Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases. Natural amplification of cholinesterase genes was first found to occur in some cancer cells and in insect species subjected to evolutionary pressure by insecticides. Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. In these parasites, over-production of cholinesterase-like proteins in secreted products and the saliva are presumed to have effector roles related to host infection. These amplification events raise questions about the role of the amplified gene products, and the adaptation processes necessary to preserve efficient cholinergic transmission. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
authors.affiliation: Dynamique Musculaire et Métabolisme, INRA, Université Montpellier, Place Viala, Montpellier France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chatonnet
authors.affiliation: Dynamique Musculaire et Métabolisme, INRA, Université Montpellier, Place Viala, Montpellier France.|Aix-Marseille Université / Centre National de la Recherche Scientifique, Architecture et Fonction des Macromolécules Biologiques laboratory, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lenfant
authors.affiliation: Aix-Marseille Université / Centre National de la Recherche Scientifique, Architecture et Fonction des Macromolécules Biologiques laboratory, Marseille, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Marchot
authors.affiliation: Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Murray E
authors.initials: ME
authors.lastname: Selkirk
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping / Q000379:methods; D005784:Gene Amplification / Q000187:drug effects* / Q000502:physiology; D023281:Genomics; D006801:Humans
chemical_list: D002800:Cholinesterase Inhibitors; D002265:Carboxylic Ester Hydrolases; D002802:Cholinesterases
keywords: acetylcholinesterase; amplification; butyrylcholinesterase; carboxylesterase; nematode; tick; α/β-hydrolase fold proteins