Ecology and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495, Japan;
Ecology and Evolution Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa, 904-0495, Japan.
Proc Natl Acad Sci U S A. 2021 Apr 6;118(14). doi: 10.1073/pnas.2021311118.
Oral venom systems evolved multiple times in numerous vertebrates enabling the exploitation of unique predatory niches. Yet how and when they evolved remains poorly understood. Up to now, most research on venom evolution has focused strictly on the toxins. However, using toxins present in modern day animals to trace the origin of the venom system is difficult, since they tend to evolve rapidly, show complex patterns of expression, and were incorporated into the venom arsenal relatively recently. Here we focus on gene regulatory networks associated with the production of toxins in snakes, rather than the toxins themselves. We found that overall venom gland gene expression was surprisingly well conserved when compared to salivary glands of other amniotes. We characterized the "metavenom network," a network of ∼3,000 nonsecreted housekeeping genes that are strongly coexpressed with the toxins, and are primarily involved in protein folding and modification. Conserved across amniotes, this network was coopted for venom evolution by exaptation of existing members and the recruitment of new toxin genes. For instance, starting from this common molecular foundation, lizards, shrews, and solenodon, evolved venoms in parallel by overexpression of kallikreins, which were common in ancestral saliva and induce vasodilation when injected, causing circulatory shock. Derived venoms, such as those of snakes, incorporated novel toxins, though still rely on hypotension for prey immobilization. These similarities suggest repeated cooption of shared molecular machinery for the evolution of oral venom in mammals and reptiles, blurring the line between truly venomous animals and their ancestors.
口腔毒液系统在众多脊椎动物中多次进化，使它们能够利用独特的捕食生态位。然而，它们是如何以及何时进化的仍然知之甚少。到目前为止，大多数关于毒液进化的研究都严格集中在毒素上。然而，使用现代动物中存在的毒素来追踪毒液系统的起源是困难的，因为它们往往进化得很快，表现出复杂的表达模式，并且是最近才被纳入毒液武器库的。在这里，我们关注的是与蛇类毒素产生相关的基因调控网络，而不是毒素本身。我们发现，与其他羊膜动物的唾液腺相比，毒液腺的基因表达总体上惊人地保守。我们描述了“元毒液网络”，这是一个由约 3000 个非分泌管家基因组成的网络，这些基因与毒素强烈共表达，主要参与蛋白质折叠和修饰。在羊膜动物中保守的是，这个网络通过对现有成员的适应和新毒素基因的招募，被用于毒液进化。例如，从这个共同的分子基础出发，蜥蜴、鼩鼱和星鼻鼹通过对激肽原的过度表达平行进化出毒液，激肽原在祖先的唾液中很常见，注射后会引起血管扩张，导致循环休克。衍生毒液，如蛇类的毒液，包含新的毒素，但仍依赖低血压来使猎物瘫痪。这些相似之处表明，在哺乳动物和爬行动物的口腔毒液进化过程中，共享的分子机制被反复利用，从而模糊了真正有毒动物与其祖先之间的界限。
