Rapid molecular evolution of pain insensitivity in multiple African rodents
Rapid molecular evolution of pain insensitivity in multiple African rodents
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DOI：
10.1126/science.aau0236
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发表时间：
2019-05-31
期刊：
影响因子：
56.9
通讯作者：
Lewin, Gary R.
中科院分区：
文献类型：
--
作者：
Eigenbrod, Ole;Debus, Karlien Y.;Lewin, Gary R.
被称为藻原的有毒物质会引起疼痛，被植物和带刺的昆虫用作防御武器。我们通过筛选与裸鼹鼠相关的8种非洲啮齿动物，用辣椒素、酸（氯化氢，pH为3.5）和异硫氰酸烯丙酯（AITC）筛选了4种以前未知的藻原不敏感的实例。利用RNA测序，我们追踪了伴随氧不敏感的转导通道中序列变异的出现，如瞬时受体电位通道TRPA1和电压门控钠通道Na(v)1.7。此外，AITC不敏感的高原野鼹鼠表现出泄漏通道NALCN（钠泄漏通道，非选择性）的过表达，从而消除了伤害感受器对AITC的检测。这些分子变化可能使高原鼹鼠对纳塔尔滴尾蚁的叮咬免疫。我们的研究揭示了如何将进化作为一种发现工具来发现关闭疼痛的分子机制。
Noxious substances, called algogens, cause pain and are used as defensive weapons by plants and stinging insects. We identified four previously unknown instances of algogen-insensitivity by screening eight African rodent species related to the naked mole-rat with the painful substances capsaicin, acid (hydrogen chloride, pH 3.5), and allyl isothiocyanate (AITC). Using RNA sequencing, we traced the emergence of sequence variants in transduction channels, like transient receptor potential channel TRPA1 and voltage-gated sodium channel Na(v)1.7, that accompany algogen insensitivity. In addition, the AITC-insensitive highveld mole-rat exhibited overexpression of the leak channel NALCN (sodium leak channel, nonselective), ablating AITC detection by nociceptors. These molecular changes likely rendered highveld mole-rats immune to the stings of the Natal droptail ant. Our study reveals howevolution can be used as a discovery tool to find molecular mechanisms that shut down pain.