Seeing the Woods for the Trees: Understanding Venom Evolution as a Guide for Biodiscovery
Seeing the Woods for the Trees: Understanding Venom Evolution as a Guide for Biodiscovery
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见树不见林：理解毒液进化作为生物发现的指南
DOI：
10.1039/9781849737876-00001
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
LOW, DOLYCHE
中科院分区：
文献类型：
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作者：
FRY, BRIAN;KOLUDAROV, IVAN;JACKSON, TIMOTHY;HOLFORD, MANDE;TERRAT, YVES;CASEWELL, NICHOLAS;UNDHEIM, EIVIND;VETTER, IRINA;ALI, SYED;LOW, DOLYCHE
发达国家和发展中国家目前使用的大多数商业药物都以天然产品为基础。这些产品大多数是基于植物，但对动物毒液的研究具有发现新的药用天然产品的巨大潜力。2，3了解毒液蛋白/肽的进化起源以及塑造当今生物多样性的力量对于有效的生物发现至关重要。此外，在药物设计和开发中有效利用毒液毒素，不能实现真正的生化，生态，形态学和药理学的多样性的毒液和相关的毒液系统的认识。迄今为止，使用毒液蛋白的一个主要限制是所研究的分类范围非常狭窄。整个有毒动物群体实际上仍然被忽视。那些被检查过的毒液显然是因为它们的医学意义或容易收集而被选择的，而不是因为它们的生态或进化独特性。毒液被定义为“一种分泌物，在一种动物的专门腺体中产生，并通过伤口的刺激传递给目标动物（无论多么微小），其中含有破坏受害者正常生理或生化过程的分子，以便于生产动物进食或防御”。[4]这一定义包括通常被认为有毒的生物（如蝎子、蛇和蜘蛛）以及传统上不被认为有毒的动物（如水蛭、蜱和吸血蝙蝠）。承认所有这些动物中毒素的募集和使用的进化类比增加了毒液独立进化的已知独立场合的数量。此外，这一认识提高了我们对毒液及其相关蛋白质进化背后因素的理解，同时也引起了对大量未经研究的毒素的关注。毒液是各种动物进化史上的一个关键创新。即使使用传统的毒液定义，人们也认为毒液系统在现存谱系中至少有20次是独立进化的（图1.1）。有趣的化石证据也引发了人们对以兽脚亚目恐龙中国鸟龙5和已灭绝的潘托列蒂科哺乳动物Bisonalveus browni为代表的已灭绝有毒谱系的可能性的猜测。[5]如果蜱、水蛭、吸血蝙蝠等谱系被正确地认为是有毒的，那么产生毒液的独立进化事件的数量就增加到30多个。进化选择对防御性毒液（如蜜蜂毒液和蜜蜂毒液）的压力主要是针对流线型毒液的发展，这种毒液的主要作用是立即产生强烈的局部疼痛。6-8相比之下，捕食性毒液是由一个经典的共同进化的军备竞赛，在那里不断发展的毒液抵抗猎物和新的毒液成分的演变施加相互的选择压力，在符合红皇后假说的情况下，货车瓦伦。9强大
The majority of commercial drugs being used today in both developed and developing countries are based on natural products. 1 Most of these products are based upon plants, but research into animal venoms holds great potential for the discovery of novel medicinally useful natural products. 2, 3 Knowledge of the evolutionary origins of venom proteins/peptides and the forces shaping the biodiversity seen today is crucial for efficient biodiscovery. In addition, efficient utilisation of venom toxins in drug design and development cannot be achieved without recognition of the true biochemical, ecological, morphological, and pharmacological diversity of venoms and associated venom systems. A major limitation of the use of venom proteins thus far has been the very narrow taxonomical range studied. Entire groups of venomous animals remain virtually ignored. Those that have been examined have apparently been selected due to their medical signi cance or ease of collection, rather than as a result of their ecological or evolutionary uniqueness.Venom is de ned as “a secretion, produced in a specialised gland in one animal and delivered to a target animal through the in iction of a wound (regardless of how tiny it may be), which contains molecules that disrupt normal physiological or biochemical processes in the victim so as to facilitate feeding or defence by the producing animal”. 4 This de nition encompasses creatures normally considered venomous (eg, scorpions, snakes, and spiders) as well as animals that have not been traditionally recognised as such (eg, leeches, ticks, and vampire bats). Acknowledgement of the evolutionary analogy of the recruitment and use of toxins in all these animals increases the number of known independent occasions in which venom has evolved independently. In addition, this acknowledgement improves our understanding of the factors underlying the evolution of venoms and their associated proteins while also drawing attention to the vast pool of unstudied toxins. Venom has been a key innovation in the evolutionary history of an incredibly diverse range of animals. Even using the traditional de nition of venom, venom systems are believed to have evolved independently on at least 20 occasions in extant lineages (Figure 1.1). Intriguing fossil evidence has also led to speculation about the possibility of extinct venomous lineages represented by the theropod dinosaur Sinornithosaurus5 and the extinct pantolestid mammal Bisonalveus browni. 5 If lineages such as ticks, leeches, vampire bats, etc. are rightfully recognised as venomous, the number of independent evolutionary events in which venom has arisen increases to over 30. The evolutionary selection pressure upon defensive venoms (eg, those of sh and bees) is largely directed at the development of streamlined venom that has the primary action of immediate, intense localised pain. 6–8 In contrast, predatory venoms are shaped by a classic co-evolutionary arms race, where evolving venom resistance in prey and the evolution of novel venom composition exerts reciprocal selective pressures on one another in a situation that conforms to the Red Queen hypothesis of Van Valen. 9 Powerful