RUI: Evolution of Acetylcholinesterase

乙酰胆碱酯酶（Acetylcholinesterase, AChE）是一种在神经和肌肉之间的交流中起重要作用的酶，它能分解运动神经释放的化学神经递质乙酰胆碱，并终止其作用。丁基胆碱酯酶（BuChE）是一种与之关系密切的酶，其功能至今仍不清楚。这两种酶都存在于高等脊索动物（脊椎动物）中。主要研究者发现文昌鱼的胆碱酯酶（ChE）是一种原始脊索动物，具有AChE和BuChE的中间性质。首席研究员认为，这种ChE类似于祖先的酯酶，AChE和BuChE是脊索动物进化早期基因复制事件的结果，随后这两种酶在结构和功能上出现了分歧。首席研究员计划通过使用生化和药理学技术来研究三种原始生物（agnathan脊椎动物Petromyzon，头脊索动物amphioxus和尾脊索动物Ciona）的ChE活性，并通过使用重组DNA技术来研究这些酶的编码基因来研究这一假设。它们的序列与高等生物的AChE和BuChE基因相似。这些研究将提供这些生物在蛋白质和核酸水平上的胆碱酯酶的详细图像，并应提供有关酶的进化，结构/功能关系和遗传调控的信息。

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.