蜘蛛毒液是一种复杂的酶混合物,多胺,无机盐和富含二硫化物的肽(DRP)。尽管DRP分布广泛且丰富,它们的进化起源仍然难以捉摸。这种知识差距源于DRP的广泛分子差异以及缺乏来自不同谱系的序列和结构数据。通过在全面的系统发育下评估DRP,结构和进化框架,我们不仅确定了78个新的蜘蛛毒素超家族,而且为它们的共同起源提供了第一个证据。我们将这些毒素超家族的起源追溯到一个原始结-我们将其命名为“AdiShakti”,根据印度教神话,宇宙的创造者-375MYA在Araneomorphae和Mygalomorphae的共同祖先中。由于正在评估的谱系占现存蜘蛛的近60%,我们的发现为蜘蛛毒液库的早期进化和多样化提供了令人着迷的见解。几乎所有蜘蛛对单一分子毒素支架的依赖与大多数其他有毒动物形成鲜明对比,这些动物已经招募了具有独立起源的多种毒素。通过比较评估araneomorph和mygalomorph蜘蛛毒液毒素的分子进化史,我们强调了它们对比的进化多样化率。我们的结果还表明,毒液的部署(例如,猎物捕获或自卫)影响DRP毒素超家族的进化多样化。
Spider venoms are a complex concoction of enzymes, polyamines, inorganic salts, and disulfide-rich peptides (DRPs). Although DRPs are widely distributed and abundant, their bevolutionary origin has remained elusive. This knowledge gap stems from the extensive molecular divergence of DRPs and a lack of sequence and structural data from diverse lineages. By evaluating DRPs under a comprehensive phylogenetic, structural and evolutionary framework, we have not only identified 78 novel spider toxin superfamilies but also provided the first evidence for their common origin. We trace the origin of these toxin superfamilies to a primordial knot - which we name \'Adi Shakti\', after the creator of the Universe according to Hindu mythology - 375 MYA in the common ancestor of Araneomorphae and Mygalomorphae. As the lineages under evaluation constitute nearly 60% of extant spiders, our findings provide fascinating insights into the early evolution and diversification of the spider venom arsenal. Reliance on a single molecular toxin scaffold by nearly all spiders is in complete contrast to most other venomous animals that have recruited into their venoms diverse toxins with independent origins. By comparatively evaluating the molecular evolutionary histories of araneomorph and mygalomorph spider venom toxins, we highlight their contrasting evolutionary diversification rates. Our results also suggest that venom deployment (e.g. prey capture or self-defense) influences evolutionary diversification of DRP toxin superfamilies.
The majority of spiders rely on their venom to defend themselves, to hunt, or both. Armed with this formidable weapon, they have managed to conquer every continent besides Antarctica since they first emerged about 495 million years ago. A closer look at spider venoms hints at an intriguing evolutionary history which has been rarely examined so far. The venom of other animals, such as snakes or scorpions, is usually formed of a wide range of unrelated toxins; in contrast, spiders rely on a single class of proteins, known as disulfide-rich peptides, to create their deadly venom cocktail. This family of molecules is impressively diverse, with each peptide having a distinct structure and mode of action. Its origins, however, have remained elusive. To fill this knowledge gap, Shaikh and Sunagar scanned the sequences of all disulfide-rich peptides generated to date, bringing together a dataset that includes 60% of all modern-day spiders. The analyses allowed the identification of 78 new superfamilies of spider toxins. They also revealed that all existing peptides originate from a single molecule, which Shaikh and Sunagar named after the powerful Hindu goddess Adi Shakti. This ancestral toxin was present 375 million years ago in the last common ancestor of modern-day spiders. The work also highlighted that disulfide-rich peptides evolved under different pressures in various groups of spiders; this may be because some species primarily use their venom for hunting, and others for defence. While the ‘hunters’ may need to constantly acquire toxins with new roles and structures to keep their edge over their prey, those that rely on venom to protect themselves may instead benefit from relying on tried-and-tested toxins useful against a range of infrequent predators. Finally, the analyses revealed that the disulphide-rich peptides of Mygalomorphae tarantulas, which form one of the three major groups of spiders, are much more diverse than the related toxins in other spiders. The underlying reason for this difference is still unclear. Several life-saving drugs currently on the market are based on toxins first identified in the venoms of snakes, cone sails or lizards. Similar discoveries could be unlocked by better understanding the range of deadly molecules used by spiders, and how these came to be.