- a Department of Ecology, Evolution, and Behavior, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States
- b J. F. Bell Museum of Natural History, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States
- Received 17 September 2014, Revised 3 February 2015, Accepted 17 March 2015, Available online 18 March 2015
Highlights
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- We investigate the molecular basis of resistance to elapid venoms in honey badgers.
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- We used a phylogenetic approach to infer the molecular evolution of nAChR for a wide range of mammals.
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- Resistance to snake venom α-neurotoxin has evolved at least four times among mammals.
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- Honey badgers, hedgehogs, and pigs have nearly equivalent amino acid replacements.
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- Two distinct biochemical mechanisms confer α-neurotoxin resistance on mammal nAChRs.
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.
Keywords
- Convergent evolution;
- Venom resistance;
- Honey badger;
- Nicotinic acetylcholine receptor;
- Mellivora capensis
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