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Science. 2019 May 31;364(6443):852-859. doi: 10.1126/science.aau0236.

Rapid molecular evolution of pain insensitivity in multiple African rodents.

Author information

1
Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
2
Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Pretoria, Republic of South Africa.
3
University of Dar es Salaam, College of Natural and Applied Sciences, Department of Zoology and Wildlife Conservation, P.O. Box 35064, Dar es Salaam, Tanzania.
4
Pest Management Centre, Sokoine University of Agriculture, Morogoro, Tanzania.
5
Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA.
6
Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany. glewin@mdc-berlin.de.
7
NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, Berlin, Germany.

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.

PMID:
31147513
DOI:
10.1126/science.aau0236

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