相互作用的氨基酸替换使箭毒蛙能够进化出对埃博霉素的抗性。
Interacting amino acid replacements allow poison frogs to evolve epibatidine resistance.
作者信息
Tarvin Rebecca D, Borghese Cecilia M, Sachs Wiebke, Santos Juan C, Lu Ying, O'Connell Lauren A, Cannatella David C, Harris R Adron, Zakon Harold H
机构信息
Department of Integrative Biology, University of Texas at Austin, Austin, TX 78712, USA.
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
出版信息
Science. 2017 Sep 22;357(6357):1261-1266. doi: 10.1126/science.aan5061.
Animals that wield toxins face self-intoxication. Poison frogs have a diverse arsenal of defensive alkaloids that target the nervous system. Among them is epibatidine, a nicotinic acetylcholine receptor (nAChR) agonist that is lethal at microgram doses. Epibatidine shares a highly conserved binding site with acetylcholine, making it difficult to evolve resistance yet maintain nAChR function. Electrophysiological assays of human and frog nAChR revealed that one amino acid replacement, which evolved three times in poison frogs, decreased epibatidine sensitivity but at a cost of acetylcholine sensitivity. However, receptor functionality was rescued by additional amino acid replacements that differed among poison frog lineages. Our results demonstrate how resistance to agonist toxins can evolve and that such genetic changes propel organisms toward an adaptive peak of chemical defense.
能够分泌毒素的动物面临着自我中毒的风险。箭毒蛙拥有多种针对神经系统的防御性生物碱。其中的一种是依博加碱，它是一种烟碱型乙酰胆碱受体（nAChR）激动剂，微克剂量即可致命。依博加碱与乙酰胆碱共享一个高度保守的结合位点，这使得在进化出抗性的同时维持nAChR功能变得困难。对人类和青蛙nAChR的电生理分析表明，在箭毒蛙中独立进化了三次的一个氨基酸替换降低了依博加碱敏感性，但代价是乙酰胆碱敏感性降低。然而，不同箭毒蛙谱系中不同的额外氨基酸替换挽救了受体功能。我们的研究结果证明了对激动剂毒素的抗性是如何进化的，以及这种基因变化如何推动生物体达到化学防御的适应峰值。
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