Zhang Zhiwei, Li Qian, Li Hao, Wei Shichao, Yu Wen, Peng Zhaojie, Wei Fuwen, Zhou Wenliang
Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, China.
Key Laboratory of Conservation and Application in Biodiversity of South China, School of Life Sciences, Guangzhou University, Guangzhou, China.
BMC Genomics. 2024 Dec 18;25(1):1210. doi: 10.1186/s12864-024-11149-6.
Animal venom systems are considered as valuable model for investigating the molecular mechanisms underlying phenotypic evolution. Stonefish are the most venomous and dangerous fish because of severe human envenomation and occasionally fatalities, whereas the genomic background of their venom has not been fully explored compared with that in other venomous animals.
In this study, we followed modern venomic pipelines to decode the Synanceia verrucosa venom components. A catalog of 478 toxin genes was annotated based on our assembled chromosome-level genome. Integrative analysis of the high-quality genome, the transcriptome of the venom gland, and the proteome of crude venom revealed mechanisms underlying the venom complexity in S. verrucosa. Six tandem-duplicated neoVTX subunit genes were identified as the major source for the neoVTX protein production. Further isoform sequencing revealed massive alternative splicing events with a total of 411 isoforms demonstrated by the six genes, which further contributed to the venom diversity. We then characterized 12 dominantly expressed toxin genes in the venom gland, and 11 of which were evidenced to produce the venom protein components, with the neoVTX proteins as the most abundant. Other major venom proteins included a presumed CRVP, Kuntiz-type serine protease inhibitor, calglandulin protein, and hyaluronidase. Besides, a few of highly abundant non-toxin proteins were also characterized and they were hypothesized to function in housekeeping or hemostasis maintaining roles in the venom gland. Notably, gastrotropin like non-toxin proteins were the second highest abundant proteins in the venom, which have not been reported in other venomous animals and contribute to the unique venom properties of S. verrucosa.
The results identified the major venom composition of S. verrucosa, and highlighted the contribution of neoVTX genes to the diversity of venom composition through tandem-duplication and alternative splicing. The diverse neoVTX proteins in the venom as lethal particles are important for understanding the adaptive evolution of S. verrucosa. Further functional studies are encouraged to exploit the venom components of S. verrucosa for pharmaceutical innovation.
动物毒液系统被认为是研究表型进化潜在分子机制的宝贵模型。由于石鱼会使人严重中毒甚至偶尔导致死亡，它们是最具毒性和危险性的鱼类，然而与其他有毒动物相比，其毒液的基因组背景尚未得到充分探索。
在本研究中，我们遵循现代毒液组学流程来解析疣状拟鲉的毒液成分。基于我们组装的染色体水平基因组，注释了一个包含478个毒素基因的目录。对高质量基因组、毒腺转录组和粗毒液蛋白质组的综合分析揭示了疣状拟鲉毒液复杂性的潜在机制。六个串联重复的新毒素（neoVTX）亚基基因被确定为新毒素蛋白产生的主要来源。进一步的异构体测序揭示了大量的可变剪接事件，这六个基因共展示了411种异构体，进一步增加了毒液的多样性。然后我们鉴定了毒腺中12个主要表达的毒素基因，其中11个被证明产生毒液蛋白成分，新毒素蛋白含量最为丰富。其他主要的毒液蛋白包括一种推测的CRVP、库尼茨型丝氨酸蛋白酶抑制剂、钙腺蛋白和透明质酸酶。此外，还鉴定了一些高度丰富的非毒素蛋白，推测它们在毒腺中发挥维持基础功能或止血的作用。值得注意的是，胃促生长素样非毒素蛋白是毒液中含量第二高的蛋白，在其他有毒动物中尚未见报道，这也赋予了疣状拟鲉独特的毒液特性。
研究结果确定了疣状拟鲉的主要毒液成分，并强调了新毒素基因通过串联重复和可变剪接对毒液成分多样性的贡献。毒液中多样的新毒素蛋白作为致死因子对于理解疣状拟鲉的适应性进化很重要。鼓励开展进一步的功能研究，以利用疣状拟鲉的毒液成分进行药物创新。
