Rapid molecular evolution of pain insensitivity in multiple African rodents

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Authors

Eigenbrod, Ole
Debus, Karlien Y.
Reznick, Jane
Bennett, Nigel Charles
Sanchez-Carranza, Oscar
Omerbasic, Damir
Hart, Daniel William
Barker, Alison J.
Zhong, Wei
Lutermann, Heike

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Publisher

American Association for the Advancement of Science

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 Nav1.7, 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.

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Keywords

Heterocephalus glaber, Hexapoda, Rattus, Rodentia, Algogens, Allyl isothiocyanate (AITC), African rodents, Pain insensitivity

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Citation

Eigenbrod, O., Debus, K.Y., Reznick, J. et al. 2019, 'Rapid molecular evolution of pain insensitivity in multiple African rodents', Science, vol, 364, no. 6443, pp. 852-859.