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Rapid molecular evolution of pain insensitivity in multiple African rodents

Item Type:Article
Title:Rapid molecular evolution of pain insensitivity in multiple African rodents
Creators Name:Eigenbrod, O. and Debus, K.Y. and Reznick, J. and Bennett, N.C. and Sánchez-Carranza, O. and Omerbašić, D. and Hart, D.W. and Barker, A.J. and Zhong, W. and Lutermann, H. and Katandukila, J.V. and Mgode, G. and Park, T.J. and Lewin, G.R.
Abstract: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 how evolution can be used as a discovery tool to find molecular mechanisms that shut down pain.
Keywords:Binding Sites, Capsaicin, Hydrochloric Acid, Insect Bites and Stings, Isothiocyanates, Molecular Evolution, NAV1.7 Voltage-Gated Sodium Channel, Nociceptive Pain, Nociceptors, Pain Threshold, Protein Conformation, RNA Sequence Analysis, Species Specificity, TRPA1 Cation Channel, Animals, Mole Rats
Publisher:American Association for the Advancement of Science
Page Range:852-859
Date:31 May 2019
Official Publication:https://doi.org/10.1126/science.aau0236
PubMed:View item in PubMed

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