Lister Callum, Arbuckle Kevin, Jackson Timothy N W, Debono Jordan, Zdenek Christina N, Dashevsky Daniel, Dunstan Nathan, Allen Luke, Hay Chris, Bush Brian, Gillett Amber, Fry Bryan G
Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia, QLD, Australia.
Department of Biosciences, College of Science, Swansea University, Swansea SA2, 8PP, UK.
Comp Biochem Physiol C Toxicol Pharmacol. 2017 Nov;202:39-54. doi: 10.1016/j.cbpc.2017.07.005. Epub 2017 Jul 27.
A paradigm of venom research is adaptive evolution of toxins as part of a predator-prey chemical arms race. This study examined differential co-factor dependence, variations relative to dietary preference, and the impact upon relative neutralisation by antivenom of the procoagulant toxins in the venoms of a clade of Australian snakes. All genera were characterised by venoms rich in factor Xa which act upon endogenous prothrombin. Examination of toxin sequences revealed an extraordinary level of conservation, which indicates that adaptive evolution is not a feature of this toxin type. Consistent with this, the venoms did not display differences on the plasma of different taxa. Examination of the prothrombin target revealed endogenous blood proteins are under extreme negative selection pressure for diversification, this in turn puts a strong negative selection pressure upon the toxins as sequence diversification could result in a drift away from the target. Thus this study reveals that adaptive evolution is not a consistent feature in toxin evolution in cases where the target is under negative selection pressure for diversification. Consistent with this high level of toxin conservation, the antivenom showed extremely high-levels of cross-reactivity. There was however a strong statistical correlation between relative degree of phospholipid-dependence and clotting time, with the least dependent venoms producing faster clotting times than the other venoms even in the presence of phospholipid. The results of this study are not only of interest to evolutionary and ecological disciplines, but also have implications for clinical toxinology.
毒液研究的一个范例是毒素的适应性进化，这是捕食者 - 猎物化学军备竞赛的一部分。本研究考察了澳大利亚蛇类一个进化枝毒液中促凝毒素对辅因子的不同依赖性、相对于饮食偏好的差异以及抗蛇毒血清对其相对中和作用的影响。所有属的特征都是富含作用于内源性凝血酶原的Xa因子的毒液。对毒素序列的检查揭示了极高的保守水平，这表明适应性进化不是这类毒素的特征。与此一致的是，毒液在不同分类群的血浆上没有表现出差异。对凝血酶原靶点的检查表明，内源性血液蛋白在多样化方面受到极端的负选择压力，这反过来又对毒素施加了强大的负选择压力，因为序列多样化可能导致偏离靶点。因此，本研究表明，在靶点因多样化而受到负选择压力的情况下，适应性进化不是毒素进化中的一致特征。与此高水平的毒素保守性一致，抗蛇毒血清表现出极高水平的交叉反应性。然而，磷脂依赖性程度与凝血时间之间存在很强的统计相关性，即使在存在磷脂的情况下，依赖性最小的毒液产生的凝血时间也比其他毒液更快。本研究结果不仅对进化和生态学科具有重要意义，而且对临床毒素学也有启示。
