Why the honey badger don't care: Convergent evolution of venom-targeted nicotinic acetylcholine receptors in mammals that survive venomous snake bites

Toxicon : Official Journal of the International Society on Toxinology
Danielle H DrabeckSharon A Jansa

Abstract

Honey badgers (Mellivora capensis) prey upon and survive bites from venomous snakes (Family: Elapidae), but the molecular basis of their venom resistance is unknown. The muscular nicotinic cholinergic receptor (nAChR), targeted by snake α-neurotoxins, has evolved in some venom-resistant mammals to no longer bind these toxins. Through phylogenetic analysis of mammalian nAChR sequences, we show that honey badgers, hedgehogs, and pigs have independently acquired functionally equivalent amino acid replacements in the toxin-binding site of this receptor. These convergent amino acid changes impede toxin binding by introducing a positively charged amino acid in place of an uncharged aromatic residue. In venom-resistant mongooses, different replacements at these same sites are glycosylated, which is thought to disrupt binding through steric effects. Thus, it appears that resistance to snake venom α-neurotoxin has evolved at least four times among mammals through two distinct biochemical mechanisms operating at the same sites on the same receptor.

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Citations

Sep 16, 2015·Proceedings of the National Academy of Sciences of the United States of America·Beata UjvariThomas Madsen
Jul 23, 2016·Integrative and Comparative Biology·Matthew L HoldingH Lisle Gibbs
Nov 8, 2017·Toxins·Michal LinialDan Ofer
Oct 20, 2017·Genome Biology and Evolution·Steven D AirdAlexander S Mikheyev
Jun 19, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hiroshi Ogawara
Feb 22, 2017·The Biochemical Journal·Juan J Calvete
Apr 5, 2020·Drug Testing and Analysis·Mark TimmsRohan Steel
Aug 18, 2020·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Spencer GreeneUNKNOWN ToxIC Snakebite Study Group
Aug 28, 2020·Allergy·David I PritchardPiers D Mitchell
Jun 25, 2021·Journal of Chemical Ecology·Caroline Fabri Bittencourt RodriguesBryan Grieg Fry

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