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.蛇类毒液组分的变异是一种普遍存在的现象，既发生于种间，也存在于种内。毒液变异会对蛇咬伤患者造成严重后果：抗蛇毒血清（antivenoms）中的特异性抗体无法识别不同蛇毒中的异种毒素（heterologous toxins），进而失效。不同蛇类支系中毒素编码基因家族的快速进化扩张，曾被广泛认为是毒液组分变异的主要诱因。然而，这一观点过于简化，忽视了尚未得到充分研究的、作用于基因转录与翻译的过程对毒液蛋白质组（venom proteome）生成的影响。本研究针对6种近缘蝰科蛇类（Viperidae）的毒液组分展开分析，比较了其毒素基因数量、毒腺中毒素基因的转录水平，以及毒素翻译为毒液分泌蛋白的情况的种间差异。研究结果显示，多级调控机制是造成近缘蛇类间毒液组分差异的核心原因。本研究证实，毒素转录、翻译水平的差异以及毒素的翻译后修饰（posttranslational modification），会对最终形成的毒液蛋白混合物产生显著影响。值得注意的是，这些过程对不同蛇类体内的不同毒素旁系同源基因（paralogs）的调控程度各不相同，因此在产生组分差异化的毒液蛋白质组方面，其重要性或许不亚于祖先基因的重复事件。本研究结果还表明，这些调控过程同样可能改变蛇毒的毒性，并阐明了这种毒液组分的变异如何削弱了被忽视的热带疾病——蛇咬伤的临床治疗效果。