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How snakes and insects outsmart deadly toxins in their prey

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Colombian snakes reveal toxin-avoidance tactics in the wild

Ten royal ground snakes from the Colombian Amazon, starved for days in captivity, were offered a dangerous meal: three-striped poison dart frogs, whose skin contains lethal histrionicotoxins, pumiliotoxins, and decahydroquinolines. Six refused the toxic feast, but four attempted to eat-first dragging the frogs along the ground, likely to reduce toxin exposure, researchers observed.

Three of the four snakes survived, suggesting their bodies could neutralize or tolerate the remaining toxins. The study, led by biologist Valeria Ramírez Castañeda of the University of California, Berkeley, highlights one of many evolutionary strategies animals use to handle deadly chemicals in their environment.

Toxins as an evolutionary arms race

Toxins have shaped ecosystems for hundreds of millions of years, originating in microbes before being adopted by animals and plants for defense or predation. In response, prey and predators alike have developed countermeasures-some even repurposing toxins for their own survival.

"A single milligram of a compound can reshape entire biological communities," said evolutionary biologist Rebecca Tarvin, also of UC Berkeley, who co-authored the snake study and reviewed toxin-resistance strategies in the 2023 Annual Review of Ecology, Evolution, and Systematics.

How animals acquire-and resist-toxins

Species become toxic through three primary routes:

  • Self-production: Bufonid toads, for example, synthesize cardiac glycosides, which disrupt ion transport in cells, halting muscle contractions and nerve signals.
  • Symbiosis: Pufferfish harbor bacteria that produce tetrodotoxin, making their flesh deadly if ingested.
  • Dietary absorption: Poison dart frogs accumulate toxins from mites and insects they consume.

To avoid self-poisoning, toxic animals often modify the proteins targeted by their own toxins. Insects feeding on milkweed, rich in cardiac glycosides, have evolved resistant sodium-potassium pumps. However, this resistance can reduce the pump's efficiency-a trade-off with potentially severe consequences in nerve cells, where precise ion balance is critical.

Workarounds in the wild

Molecular biologist Susanne Dobler of Hamburg University studies the large milkweed bug, which consumes milkweed seeds. Her 2023 research revealed that while the bug's brain retains a toxin-sensitive (but highly functional) version of the sodium-potassium pump, other body parts use resistant variants. She suspects ABCB transporter proteins-which expel cellular waste-may shield the brain by ejecting glycosides before they cause harm.

Dobler's team also hypothesizes that ABCB transporters in gut membranes prevent toxins from entering the body altogether. The red onion beetle, which feeds on toxic lily of the valley, exemplifies this: it excretes glycosides unchanged, and its toxin-laden feces even deter ant predators.

Liver enzymes and 'toxin sponges'

Royal ground snakes may rely on their livers to detoxify frog poisons. Tarvin's team found that snake liver extracts can neutralize the frogs' toxins, possibly via enzymes that break down harmful compounds-similar to how humans metabolize alcohol. Alternatively, the livers might produce "toxin sponge" proteins that bind and neutralize poisons, a strategy also seen in poison frogs resistant to saxitoxin.

California ground squirrels use a comparable tactic against rattlesnake venom. Their blood contains proteins that block venom components, mirroring the snakes' own self-protection mechanisms. Evolutionary biologist Matthew Holding of the University of Michigan notes that this defense is locally adapted: squirrel antivenom matches the venom profiles of nearby rattlesnake populations.

Limits of resistance

Even adapted species aren't invincible. Rattlesnakes continuously evolve new venom variants to overcome squirrel resistance, and a snake can still die from its own venom in high doses. Many animals thus prioritize avoidance: ground snakes drag frogs to reduce toxin contact, turtles eat only the safer belly skin of toxic newts, and monarch caterpillars drain milkweed veins before feeding.

Repurposing poisons for defense

Some creatures not only survive toxins but weaponize them. The iridescent dogbane beetle, for instance, relocates cardiac glycosides from its host plants to its back, secreting droplets as a deterrent when threatened. "Annoy them, and you'll see toxins bead up on their wing cases," Dobler said.

This interdependence can create far-reaching ecological links. A 2021 study by Noah Whiteman of UC Berkeley traced how milkweed toxins influence the black-headed grosbeak, a bird that preys on monarch butterflies in Mexican forests. "A plant toxin from an Ontario prairie ends up shaping a bird's biology thousands of miles away," Whiteman marveled. "The evolutionary ripple effects are staggering."

"It's just amazing-the journey traveled by this small molecule, and the influence that it has on evolution."

Noah Whiteman, evolutionary biologist, UC Berkeley

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