Widespread Evolution of Molecular Resistance to Snake Venom α-Neurotoxins in Vertebrates.
Toxins (Basel)
; 12(10)2020 10 02.
Article
in En
| MEDLINE
| ID: mdl-33023159
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Snake Bites
/
Snake Venoms
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Snakes
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Drug Resistance
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Receptors, Nicotinic
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Nicotinic Antagonists
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Evolution, Molecular
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Neuromuscular Junction
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Neurotoxins
Limits:
Animals
Language:
En
Journal:
Toxins (Basel)
Year:
2020
Document type:
Article
Affiliation country: