Tracking toxins in venomous Vermes: comparative venomics of polychaete annelids

虽然大多数外行人在识别水母、黄蜂、蜘蛛和蝎子等生物是潜在危险的有毒生物方面没有什么问题，但知道标志性动物如科莫多龙或不起眼的蜈蚣拥有强大毒液的人要少得多。同样，尽管在美国东北部和加拿大的海岸挖出血虫--一群海洋多毛类环节动物--作为鱼饵是一项耗资数百万美元的家庭手工业，但毫无戒心的渔民是否意识到，他们钓的是含有强烈神经毒性毒液的蠕虫，这一点值得怀疑。血虫和几类相关的鳞虫有两对坚硬的下巴，与毒腺有关。虽然这些毒液在驯服猎物的过程中可能在动物的生活中扮演着至关重要的角色，但我们几乎对它们的毒液的组成一无所知。这不仅给我们对一个重要的有机体群体--可能代表多达1000种有毒蠕虫--的理解留下了很大的漏洞，而且还损害了我们对毒液生物学和动物界进化的一般理解。这项研究旨在通过对多毛类毒素的组成进行第一次广泛而深入的分析来弥补这种忽视。该项目使用尖端技术的组合来在遗传和蛋白质水平上确定毒素的组成。选择了8种蠕虫--4种血虫和4种鳞虫--以代表它们所代表的主要群体的横截面。对于每个物种，将描述多达50万个mRNA序列。这些前体分子是生产毒素蛋白的模板。此外，毒素蛋白本身也将直接从提取的毒液中检测出来。这些数据将揭示蠕虫毒腺中表达的毒素，为阐明已知存在于血虫毒液中的一种毒素的准确身份提供重要贡献。这一点很重要，因为这种毒素有一种非常特殊的作用模式--在野外麻痹和杀死甲壳类猎物--这对在实验室研究神经过程的研究人员已经很有用。通过比较不同虫群和其他有毒动物的毒液毒素，我们也可以开始解决与毒液和有毒生物进化有关的重要问题。例如，毒液是收敛进化的一个主要例子，即在不同的类群中相似适应的重复独立进化。由于毒液有多次独立进化，比较它们的组成可以揭示收敛进化的运行规律。最后，毒液的突出特征和我们对它们着迷的来源，当然是它们具有的生理效应。该项目将测试蠕虫毒液的特定类型的药理活性，如神经毒性。这将有助于更好地了解生物体的生物学，但也许更重要的是，了解毒素的生物活性可以在下游有价值的应用。已经有七种处方药是从动物毒液的成分中开发出来的，这些毒液来自不同的动物，如锥螺和吉拉怪兽。由于它们被用来治疗人类的严重疾病，包括糖尿病和高血压，许多人可能会从挖掘隐藏的毒液生物多样性中受益。

Although most lay people have little problem in identifying creatures like jellyfish, wasps, spiders, and scorpions as potentially dangerous venomous organisms, far fewer know that iconic animals such as the Komodo dragon, or the inconspicuous centipedes possess potent venoms. Similarly, although digging up bloodworms-a group of marine polychaete annelids-for use as fish bait is a multi-million dollar cottage industry along the coasts of the Northeastern United States and Canada, it is doubtful whether unsuspecting fishermen realize that they are hooking worms that possess potent neurotoxic venom. Bloodworms and several groups of the related scale-worm have two pairs of hardened jaw, associated with venom gland. Although these venoms presumable play a crucial role in the life of the animals in subduing prey, we know almost nothing about the make-up of their venoms. This leaves not only a large hole in our understanding of an important group of organisms-representing possibly as many as 1,000 species of venomous worms-but it also compromises our general understanding of venom biology and evolution in the animal kingdom. This study aims to remedy this ignorance by performing the first extensive and intensive analysis of the composition of polychaete venoms.This project uses a combination of cutting edge techniques to determine venom toxin composition on both the genetic and protein levels. Eight species of worms have been selected-4 species of bloodworms and 4 species of scale-worms-to represent a cross section of the major groups they represent. For each species, up to half a million mRNA sequences will be characterized. These precursor molecules are the templates for the production of toxin proteins. In addition, the toxin proteins themselves will also be determined directly from extracted venom. Together these data will reveal what toxins are expressed in the venom glands of the worms, providing an important contribution towards elucidating the precise identity of one toxin that is known to exist in bloodworm venom. This is important because this toxin has a very specific mode of action-paralyzing and killing crustacean prey in the wild-that is already of use to researchers who study neuronal processes in the laboratory.By comparing venom toxins between different groups of worms and other venomous animals we can also start to address important questions relating to the evolution of venoms and venomous organisms. For example, venoms are a prime example of convergent evolution, the repeated independent evolution of similar adaptations in different taxa. Since venoms have evolved many times independently, a comparison of their composition can reveal shed light on the rules under which convergent evolution operates.Lastly, the outstanding feature of venoms, and the source of our fascination with them, is of course the physiological effects they have. This project will test specific types of pharmacological activities of the worm venoms, such as neurotoxity. This will lead to a better understanding of the biology of the organisms, but perhaps even more importantly, understanding the bioactivities of toxins can have valuable downstream applications. Already seven prescription drugs have been developed from components of animal venoms, from animals as different as cone snails and the Gila monster. Since these are used to treat serious conditions in humans, including diabetes and hypertension, potentially many people could benefit from mining the hidden biodiversity of venoms.