Widespread convergent evolution of alpha-neurotoxin resistance in African mammals

Abstract

Convergent evolution is central to the study of adaptation and has been used to understand both the limits of evolution and the diverse patterns and processes which result in adaptive change. Resistance to snake venom alpha-neurotoxins ( α NTXs) is a case of widespread convergence having evolved several times in snakes, lizards and mammals. Despite extreme toxicity of α NTXs, substitutions in its target, the nicotinic acetylcholine receptor (nAChR), prevent α NTX binding and render species resistant. Recently, the published meerkat (Herpestidae) genome revealed that meerkats have the same substitutions in nAChR as the venom-resistant Egyptian mongoose (Herpestidae), suggesting that venom-resistant nAChRs may be ancestral to Herpestids. Like the mongoose, many other species of feliform carnivores prey on venomous snakes, though their venom resistance has never been explored. To evaluate the prevalence and ancestry of α NTX resistance in mammals, we generate a dataset of mammalian nAChR using museum specimens and public datasets. We find five instances of convergent evolution within feliform carnivores, and an additional eight instances across all mammals sampled. Tests of selection show that these substitutions are evolving under positive selection. Repeated convergence suggests that this adaptation played an important role in the evolution of mammalian physiology and potentially venom evolution.

High-Voltage Toxin’Roll: Electrostatic Charge Repulsion as a Dynamic Venom Resistance Trait in Pythonid Snakes

“…The earliest recognized example of steric hindrance, N-glycosylation, was detected in the Egyptian Mongoose ( Herpestes ichneumon ), a predator of certain cobras [ 6 ]. This trait was later identified as a basal trait of the mongoose/meerkat family (Herpestidae), which includes several snake-consuming species [ 37 , 38 ]. This resistance method has been found to have evolved convergently across various taxa that interact with venomous snakes, including within snakes themselves, providing self-immunity against their own venom [ 37 , 38 , 39 ].…”

“…This trait was later identified as a basal trait of the mongoose/meerkat family (Herpestidae), which includes several snake-consuming species [ 37 , 38 ]. This resistance method has been found to have evolved convergently across various taxa that interact with venomous snakes, including within snakes themselves, providing self-immunity against their own venom [ 37 , 38 , 39 ]. This mutation replaces an amino acid with an asparagine (N) residue (frequently at orthosteric site positions 187 or 189), which is subsequently modified post-translationally to attach a bulky glycosylation side chain.…”

“…Electrostatic charge repulsion presents an alternate mechanism for countering snake venom, and, like steric hindrance, it has independently evolved in diverse groups, including both the prey (Burmese Python ( Python bivittatus )) and predators (such as the Honey Badger ( Mellivora capensis )) of venomous snakes [ 26 , 28 , 37 , 39 , 40 ]. The Honey Badger’s iconic resistance to cobra venom is linked to a singular mutation at the nAChR’s orthosteric site: tryptophan (W) at position 187 replaced by the positively charged arginine (R) [ 26 , 40 ].…”

A Russian Doll of Resistance: Nested Gains and Losses of Venom Immunity in Varanid Lizards

“…Steric hindrance was first described in the Egyptian Mongoose ( Herpestes ichneumon ), a predator of cobras [ 4 ], and subsequently shown to be a basal trait in the snake-eating family Herpestidae [ 25 , 26 ]. This form of resistance has been shown to have convergently evolved widely in both prey and predators of neurotoxic venomous snakes, including within the snakes themselves as a resistance against their own venoms [ 19 , 25 , 27 ].…”

“…Similar to the mechanism of steric hindrance, the electrostatic charge-repulsion form of resistance is also documented in both the natural prey and the predatory species of venomous snakes [ 22 , 26 , 28 ]. Instances of this resistance have been identified as convergently evolving in diverse creatures, including snake predators such as the honey badger ( Mellivora capensis ), various hedgehog species ( Erinaceus concolor and Erinaceus europaeus ), pigs ( Sus scrofa ), and slow moving prey of sympatric snakes such as the Burmese python, the mole snake, and caecilians [ 22 , 26 , 27 , 28 ].…”