Alistair Reid Venom Research Unit andMolecular Ecology and Evolution Group, School of Biological Sciences, Bangor University, Bangor LL57 2UW, United Kingdom; and
Bioinformatics Unit, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom;
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9205-10. doi: 10.1073/pnas.1405484111. Epub 2014 Jun 9.
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.
毒液成分的变异在蛇类中是一种普遍现象，既存在于种间，也存在于种内。毒液变异会使抗蛇毒血清中发现的特定抗体对不同毒液中的异源毒素无效，从而给蛇伤受害者带来严重后果。不同蛇类谱系中不同毒素编码基因家族的快速进化扩张被广泛认为是毒液变异的主要原因。然而，这种观点过于简单化，忽视了作用于基因转录和翻译的过程可能对毒液蛋白质组的产生产生的研究不足的影响。在这里，我们评估了六种相关蝰蛇的毒液成分，并比较了种间毒素基因数量、毒液腺中转录以及在毒液中分泌的蛋白质翻译的变化。我们的结果表明，多个调节水平负责产生相关蛇种之间毒液成分的变异。我们证明，毒素转录、翻译和翻译后的修饰水平的差异对产生的毒液蛋白混合物有很大影响。值得注意的是，这些过程在不同的蛇中对不同的毒素旁系同源物产生不同的作用程度，因此对于产生组成上不同的毒液蛋白质组可能与祖先基因复制事件一样重要。我们的结果表明，这些过程也可能导致蛇毒毒性的改变，我们展示了这种可变性如何破坏对一种被忽视的热带病，蛇咬伤的治疗。
