title: Why the honey badger don't care: Convergent evolution of venom-targeted nicotinic acetylcholine receptors in mammals that survive venomous snake bites.
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.
authors: Department of Ecology, Evolution, and Behavior, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States; J. F. Bell Museum of Natural History, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States. Electronic address: danielle.drabeck@gmail.com.
authors: Danielle H
authors: DH
authors: Drabeck
authors: Department of Ecology, Evolution, and Behavior, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States.
authors: Antony M
authors: AM
authors: Dean
authors: Department of Ecology, Evolution, and Behavior, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States; J. F. Bell Museum of Natural History, University of Minnesota, 1987 Upper Buford Circle, St. Paul, MN 55108, United States.
authors: Sharon A
authors: SA
authors: Jansa
mesh_terms: D000818:Animals; D000836:Animals, Zoo / Q000097:blood / Q000235:genetics / Q000502:physiology; D001665:Binding Sites; D030562:Databases, Protein; D018432:Drug Resistance, Multiple; D004546:Elapid Venoms / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity; D017815:Elapidae / Q000502:physiology*; D019143:Evolution, Molecular; D008024:Ligands; D008958:Models, Molecular; D045969:Mustelidae / Q000097:blood / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity; D010802:Phylogeny; D011235:Predatory Behavior; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012909:Snake Bites / Q000378:metabolism / Q000503:physiopathology / Q000662:veterinary*
chemical_list: D004546:Elapid Venoms; D008024:Ligands; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011978:Receptors, Nicotinic
keywords: Convergent evolution; Honey badger; Mellivora capensis; Nicotinic acetylcholine receptor; Venom resistance