背景:Conus,一种高度多样化的有毒捕食者,由于其丰富的神经活性肽被称为芋螺毒素,在神经科学和新药开发中引起了极大的关注。转录组的最新进展,蛋白质组,和基因组分析促进了Conus\'毒腺内螺毒素的鉴定,提供对芋螺毒素基因的遗传特征和进化模式的见解。然而,在很多情况下,人们仍然不清楚松香毒素异常高变性背后的潜在机制.
结果:我们分析了34种Conus物种的转录组,检查各种组织,如毒液管,毒液灯泡,还有唾液腺,从而鉴定了芋螺毒素基因。遗传变异分析显示,这些基因的一个子集(占总数的15.78%)在Conus物种中进行了阳性选择(Ka/Ks>1,p<0.01)。此外,我们重新组装并注释了白菊的基因组,发现221种芋螺毒素编码基因.这些基因主要由三个外显子组成,其中很大一部分在毒液导管中显示出高转录活性。重要的是,芋螺毒素基因的侧翼区和邻近内含子表现出更高的转座子元件患病率,这表明它们对在芋螺毒素中观察到的广泛变异性的潜在贡献。此外,我们在白桦梭菌中检测到基因组重复,这可能导致了芋螺毒素基因数量的增加。有趣的是,我们的研究还提供了Conus物种间基因渗入的证据,这表明种间杂交可能在塑造多种芋螺毒素基因的进化中发挥了作用。
结论:本研究强调了适应性进化和渗入杂交对芋螺毒素基因遗传多样性和Conus进化的影响。我们还提出了一个假设,表明转座因子可能对芋螺毒素中观察到的显着多样性做出了显着贡献。这些发现不仅增强了我们对肽遗传多样性的理解,而且为肽生物工程提供了一种新的方法。
BACKGROUND: Conus, a highly diverse species of venomous predators, has attracted significant attention in neuroscience and new drug development due to their rich collection of neuroactive peptides called conotoxins. Recent advancements in transcriptome, proteome, and genome analyses have facilitated the identification of conotoxins within Conus\' venom glands, providing insights into the genetic features and evolutionary patterns of
conotoxin genes. However, the underlying mechanism behind the extraordinary hypervariability of conotoxins remains largely unknown.
RESULTS: We analyzed the transcriptomes of 34 Conus species, examining various tissues such as the venom duct, venom bulb, and salivary gland, leading to the identification of
conotoxin genes. Genetic variation analysis revealed that a subset of these genes (15.78% of the total) in Conus species underwent positive selection (Ka/Ks > 1, p < 0.01). Additionally, we reassembled and annotated the genome of C. betulinus, uncovering 221
conotoxin-encoding genes. These genes primarily consisted of three exons, with a significant portion showing high transcriptional activity in the venom ducts. Importantly, the flanking regions and adjacent introns of
conotoxin genes exhibited a higher prevalence of transposon elements, suggesting their potential contribution to the extensive variability observed in conotoxins. Furthermore, we detected genome duplication in C. betulinus, which likely contributed to the expansion of conotoxin gene numbers. Interestingly, our study also provided evidence of introgression among Conus species, indicating that interspecies hybridization may have played a role in shaping the evolution of diverse
conotoxin genes.
CONCLUSIONS: This study highlights the impact of adaptive evolution and introgressive hybridization on the genetic diversity of conotoxin genes and the evolution of Conus. We also propose a hypothesis suggesting that transposable elements might significantly contribute to the remarkable diversity observed in conotoxins. These findings not only enhance our understanding of peptide genetic diversity but also present a novel approach for peptide bioengineering.