Venom Evolution Laboratory, School of Biological Sciences, University of Queensland, St. Lucia, Queensland, Australia.
Mol Cell Proteomics. 2013 Jul;12(7):1881-99. doi: 10.1074/mcp.M112.023143. Epub 2013 Apr 1.
Although it has been established that all toxicoferan squamates share a common venomous ancestor, it has remained unclear whether the maxillary and mandibular venom glands are evolving on separate gene expression trajectories or if they remain under shared genetic control. We show that identical transcripts are simultaneously expressed not only in the mandibular and maxillary glands, but also in the enigmatic snake rictal gland. Toxin molecular frameworks recovered in this study were three-finger toxin (3FTx), CRiSP, crotamine (beta-defensin), cobra venom factor, cystatin, epididymal secretory protein, kunitz, L-amino acid oxidase, lectin, renin aspartate protease, veficolin, and vespryn. We also discovered a novel low-molecular weight disulfide bridged peptide class in pythonid snake glands. In the iguanian lizards, the most highly expressed are potentially antimicrobial in nature (crotamine (beta-defensin) and cystatin), with crotamine (beta-defensin) also the most diverse. However, a number of proteins characterized from anguimorph lizards and caenophidian snakes with hemotoxic or neurotoxic activities were recruited in the common toxicoferan ancestor and remain expressed, albeit in low levels, even in the iguanian lizards. In contrast, the henophidian snakes express 3FTx and lectin toxins as the dominant transcripts. Even in the constricting pythonid and boid snakes, where the glands are predominantly mucous-secreting, low-levels of toxin transcripts can be detected. Venom thus appears to play little role in feeding behavior of most iguanian lizards or the powerful constricting snakes, and the low levels of expression argue against a defensive role. However, clearly the incipient or secondarily atrophied venom systems of these taxa may be a source of novel compounds useful in drug design and discovery.
尽管已经确定所有的有鳞目蜥蜴类动物都有一个共同的有毒祖先，但仍然不清楚上颌和下颌毒腺是在独立的基因表达轨迹上进化，还是仍然受到共同的遗传控制。我们表明，相同的转录本不仅在颌骨和上颌腺中同时表达，而且在神秘的蛇类的 rictal 腺中也同时表达。在这项研究中回收的毒素分子框架是三指毒素（3FTx）、CRiSP、crotamine（β-防御素）、眼镜蛇毒液因子、半胱氨酸蛋白酶抑制剂、附睾分泌蛋白、kunitz、L-氨基酸氧化酶、凝集素、天冬氨酸蛋白酶、vespicolin 和 vespryn。我们还在 pythonid 蛇腺中发现了一种新的低分子量二硫键桥接肽类。在鬣蜥目中，表达水平最高的是具有潜在抗菌作用的物质（crotamine（β-防御素）和半胱氨酸蛋白酶抑制剂），其中 crotamine（β-防御素）的多样性也最高。然而，在 anguimorph 蜥蜴和 caenophidian 蛇中鉴定出的许多具有血液毒性或神经毒性活性的蛋白质在共同的有鳞目蜥蜴祖先中被招募，并保持表达，尽管表达水平较低，即使在鬣蜥目中也是如此。相比之下， henophidian 蛇以 3FTx 和凝集素毒素作为主要转录本。即使在主要分泌粘液的收缩 pythonid 和 boid 蛇中，也可以检测到低水平的毒素转录本。因此，毒液似乎在大多数鬣蜥的进食行为中或在强大的收缩蛇中作用不大，低表达水平表明其不具有防御作用。然而，这些类群的初始或次生性萎缩的毒液系统显然可能是用于药物设计和发现的新型化合物的来源。
