RUI: Evolution of Acetylcholinesterase

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Acetylcholinesterase (AChE) is an enzyme that plays a very important role in the communication between nerve and muscle, by breaking down acetylcholine, the chemical neurotransmitter released by the motor nerve, and terminating its action. Butyrylcholinesterase (BuChE) is a very closely related enzyme whose function is still unknown. Both of these enzymes are present in higher chordates (vertebrates). The principal investigator found that the cholinesterase (ChE) of amphioxus, a primitive chordate, has properties intermediate to AChE and BuChE. The principal investigator suggests that this ChE resembles the ancestral esterase and that AChE and BuChE have appeared as a result of a gene duplication event early in chordate evolution, with subsequent structural and functional divergence of the two enzymes. The principal investigator plans to investigate this hypothesis by using biochemical and pharmacological techniques to study the ChE activity of three primitive organisms -- the agnathan vertebrate Petromyzon, the cephalochordate amphioxus, and the urochordate Ciona, and by using the techniques of recombinant DNA technology to investigate the genes coding for these enzymes, and their sequence similarities to the genes for AChE and BuChE from higher organisms. These studies will provide a detailed picture of the cholinesterases from these organisms at the protein and nucleic acid levels, and should provide information about the evolution, structure/function relationships, and genetic regulation of the enzyme.