Skinks Evolved "Molecular Armor" Against Snake Venom

A University of Queensland-led study has found Australian skinks have evolved molecular armour to stop snake venom from shutting down their muscles.

Professor Bryan Fry from UQ’s School of the Environment said revealing exactly how skinks dodge death could inform biomedical approaches to treating snakebite in people.

“What we saw in skinks was evolution at its most ingenious,” Professor Fry said.

“Australian skinks have evolved tiny changes in a critical muscle receptor, called the nicotinic acetylcholine receptor.

“This receptor is normally the target of neurotoxins which bind to it and block nerve-muscle communication causing rapid paralysis and death.

“But in a stunning example of a natural counterpunch, we found that on 25 occasions skinks independently developed mutations at that binding site to block venom from attaching.

“It’s a testament to the massive evolutionary pressure than venomous snakes exerted after their arrival and spread across the Australian continent, when they would have feasted on the defenceless lizards of the day.

“Incredibly, the same mutations evolved in other animals like mongooses which feed on cobras.

“We confirmed with our functional testing that Australia’s Major Skink (Bellatorias frerei) has evolved exactly the same resistance mutation that gives the honey badger it’s famous resistance to cobra venom.

“To see this same type of resistance evolve in a lizard and a mammal is quite remarkable – evolution keeps hitting the same molecular bullseye.”

The muscle receptor mutations in the skinks included a mechanism to add sugar molecules to physically block toxins and the substitution of a protein building block (amino acid arginine at position 187).

The laboratory work validating the mutations was carried out at UQ’s Adaptive Biotoxicology Laboratory by Dr Uthpala Chandrasekara who said it was incredible to witness.

“We used synthetic peptides and receptor models to mimic what happens when venom enters an animal at the molecular level and the data was crystal clear, some of the modified receptors simply didn’t respond at all,” said Dr Chandrasekara.

“It’s fascinating to think that one tiny change in a protein can mean the difference between life and death when facing a highly venomous predator.”

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The findings could one day inform the development of novel antivenoms or therapeutic agents to counter neurotoxic venoms.

“Understanding how nature neutralises venom can offer clues for biomedical innovation,” Dr Chandrasekara said.

“The more we learn about how venom resistance works in nature, the more tools we have for the design of novel antivenoms.”

Reference: Chandrasekara U, Mancuso M, Shea G, et al. Make acetylcholine great again! Australian skinks evolved multiple neurotoxin-proof nicotinic acetylcholine receptors in defiance of snake venom. Int J Mol Sci. 2025;26(15):7510. doi: 10.3390/ijms26157510

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