中科院动物所朱顺义研究组在蝎毒素物种选择性进化机制研究方面获进展，这有助于针对特定害虫的杀虫剂研发。论文日前在线发表于《Molecular Biology and Evolution》。

朱顺义告诉《中国科学报》记者，蝎作为一类有毒动物，处于食物链的中间位置。在猎物（小型昆虫等）及捕食者（老鼠等）的双重选择压力下，该物种已成功进化了同时靶向昆虫和老鼠钠通道的α-型神经毒素参与捕食和防御。虽然α-型神经毒素超强的抗虫活性（nmol级）显示其有作为杀虫剂的巨大潜能，但是它们伴随的哺乳动物毒性成为主要的制约因素，为该领域的一大挑战。

研究人员从这类毒素物种选择性的进化机制研究入手，通过选用我国宁夏产条斑钳蝎的钠通道毒素MT-5为模型，对先前发现的毒素阳性达尔文位点完成了系统性的定点突变分析。合并电生理测定技术首次鉴定了MT-5和哺乳动物钠通道rNav1.1亚型相互作用的关键热点残基。

以此为基础，研究人员构建了高质量的毒素—通道复合物的计算机模型，并建立了毒素和通道相互作用的配对残基。活体毒性测定表明，突变或删除这些热点氨基酸残基能够显著消除MT-5对小鼠的毒性，但却实质性地保留或增强了它的抗虫活性。（来源：中国科学报 马卓敏）

Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides

Abstract  Positive selection sites (PSSs), a class of amino acid sites with an excess of non-synonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e. agent of selection). Scorpion α-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na+ (Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus α-toxin family and a two-residue insertion (19AlaPhe20) located within a positively selected loop via mutational analysis of α-like MeuNaTxα-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile40 and Leu41) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti-mammalian activity in MeuNaTxα-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion α-like toxins. Based on an experiment-guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets’ diversity.

原文链接：http://mbe.oxfordjournals.org/content/early/2016/05/08/molbev.msw065.full.pdf+html