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.
Bibliographical noteFunding Information:
Thanks to the Fort Wayne Children's Zoo and the San Diego Zoo Institute for Conservation Research for providing samples of their captive Mellivora capensis for DNA extraction. Thanks to Dr Emily Latch and her graduate student Elizabeth Kierepka for providing badger tissue samples. Funding for this research was provided by a Rosemary Grant Award from the Society for the Study of Evolution (to D.D.) and by the Department of Ecology, Evolution, and Behavior at the University of Minnesota.
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- Convergent evolution
- Honey badger
- Mellivora capensis
- Nicotinic acetylcholine receptor
- Venom resistance