Data from: Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms

Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite.蛇类毒液组成的变异是一种普遍存在的生物学现象，既发生于种间（interspecifically），也存在于种内（intraspecifically）。毒液变异会对蛇伤患者造成严重不良后果：抗蛇毒血清（antivenoms）中的特异性抗体无法有效识别不同毒液中的异种毒素。此前学界普遍认为，不同蛇类谱系中毒素编码基因家族的快速进化扩张是毒液变异的主要诱因。但该观点过于简化，忽视了尚未得到充分研究的、作用于基因转录与翻译过程的因素对毒液蛋白质组（venom proteome）生成的影响。本研究针对6种亲缘关系较近的蝰科（Viperidae）蛇类的毒液组成展开分析，对比了不同物种间毒素基因的数量、其在毒腺中的转录水平，以及翻译为毒液分泌蛋白的差异。研究结果显示，多层级的调控过程是亲缘蛇类间毒液组成产生变异的核心来源。我们证实，毒素转录、翻译及翻译后修饰（posttranslational modification）的水平差异，对最终形成的毒液蛋白质混合物具有显著影响。值得注意的是，这些调控过程对不同蛇类体内不同毒素旁系同源基因（paralogs）的作用程度各不相同，因此其在催生组成迥异的毒液蛋白质组方面，重要性不亚于祖先基因复制事件。本研究结果表明，这类调控过程同样可能参与改变蛇毒的毒性，同时我们也阐明了这种变异如何会削弱针对蛇伤这一被忽视的热带病的临床治疗效果。