Convergent and parallel evolution in a voltage-gated sodium channel underlies TTX-resistance in the Greater Blue-ringed Octopus: Hapalochlaena lunulata
Convergent and parallel evolution in a voltage-gated sodium channel underlies TTX-resistance in the Greater Blue-ringed Octopus: Hapalochlaena lunulata
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DOI：
10.1016/j.toxicon.2019.09.013
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发表时间：
2019-12-01
期刊：
影响因子：
2.8
通讯作者：
Hanifin, Charles T.
中科院分区：
文献类型：
--
作者：
Geffeney, Shana L.;Williams, Becky L.;Hanifin, Charles T.
河豚毒素（TTX）的自然历史和药理学长期以来一直引起生物学家的兴趣。这种毒素具有跨越两个生命领域（细菌和真核生物）的显著分布。在真核生物中，TTX仅在动物中被发现，但已知存在于超过50种遗传学上遥远的后生动物中。尽管数十年的工作，TTX的起源和生物合成途径仍然没有得到解决。在河豚鱼和蝾螈的调查提供了深入了解收购的TTX通过电压门控钠离子通道（VGSC）的演变，降低了TTX的结合亲和力的自身抗性。到目前为止，还没有研究这些蛋白质在河豚毒素蓝环章鱼。在这里，我们报告的数据表明，大蓝环章鱼（Hapalochlaena lunulata）表达VGSC（HINa（v）1）基因的突变，降低了通道的TTX结合亲和力，并可能使生物体TTX抗性。我们在HINa（v）1的TTX结合位点鉴定了三个氨基酸取代，这可能使通道和生物体都具有TTX抗性。这些替换与其他TTX携带类群中的生物体TTX抗性相关，并且与在鱼类、蝾螈和一些TTX抗性无脊椎动物中进化的替换趋同。
The natural history and pharmacology of tetrodotoxin (TTX) has long intrigued biologists. This toxin has a remarkable distribution that spans two domains of life (Bacteria and Eukarya). Within Eukaryotes, TTX has only been identified in animals but is known to be present in over five-dozen species of phylogenetically distant Metazoans. Despite decades of work, the origin and biosynthetic pathways of TTX remain unresolved. Investigations in puffer fishes and salamanders have provided insights into the acquisition of auto-resistance to TTX through the evolution of voltage-gated sodium ion channels (VGSCs) that have reduced binding affinity for TTX. To date there have been no studies of these proteins in tetrodotoxic Blue-Ringed Octopuses. Here we report data demonstrating that the Greater Blue-ringed Octopus (Hapalochlaena lunulata) expresses a VGSC (HINa(v)1) gene with mutations that reduce the channel's TTX-binding affinity and likely render the organism TTX resistant. We identified three amino-acid substitutions in the TTX-binding site of HINa(v)1 that likely confer TTX-resistance to both the channel and the organism. These substitutions are associated with organismal TTX-resistance in other TTX-bearing taxa and are convergent with substitutions that have evolved in fish, salamanders, and some TTX-resistant invertebrates.