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- W3089624059 abstract "Venomous snakes are important subjects of study in evolution, ecology, and biomedicine. Many venomous snakes have alpha-neurotoxins (α-neurotoxins) in their venom. These toxins bind the alpha-1 nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction, causing paralysis and asphyxia. Several venomous snakes and their predators have evolved resistance to α-neurotoxins. The resistance is conferred by steric hindrance from N-glycosylated asparagines at amino acids 187 or 189, by an arginine at position 187 that has been hypothesized to either electrostatically repulse positively charged neurotoxins or sterically interfere with α-neurotoxin binding, or proline replacements at positions 194 or 197 of the nAChR ligand-binding domain to inhibit α-neurotoxin binding through structural changes in the receptor. Here, we analyzed this domain in 148 vertebrate species, and assessed its amino acid sequences for resistance-associated mutations. Of these sequences, 89 were sequenced de novo. We find widespread convergent evolution of the N-glycosylation form of resistance in several taxa including venomous snakes and their lizard prey, but not in the snake-eating birds studied. We also document new lineages with the arginine form of inhibition. Using an in vivo assay in four species, we provide further evidence that N-glycosylation mutations reduce the toxicity of cobra venom. The nAChR is of crucial importance for normal neuromuscular function and is highly conserved throughout the vertebrates as a result. Our research shows that the evolution of α-neurotoxins in snakes may well have prompted arms races and mutations to this ancient receptor across a wide range of sympatric vertebrates. These findings underscore the inter-connectedness of the biosphere and the ripple effects that one adaption can have across global ecosystems." @default.
- W3089624059 created "2020-10-08" @default.
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- W3089624059 date "2020-10-02" @default.
- W3089624059 modified "2023-10-09" @default.
- W3089624059 title "Widespread Evolution of Molecular Resistance to Snake Venom α-Neurotoxins in Vertebrates" @default.
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- W3089624059 doi "https://doi.org/10.3390/toxins12100638" @default.
- W3089624059 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7601176" @default.
- W3089624059 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33023159" @default.
- W3089624059 hasPublicationYear "2020" @default.
- W3089624059 type Work @default.