Tetrodotoxin: a potent defence for pufferfish… and other organisms

Tetrodotoxin is a lethal pufferfish defence chemical

In Japanese cuisine, the iconic pufferfish Fugu (which refers to several species) is notorious because if improperly prepared its consumption can have fatal consequences.

Takifugu rubripesSome body parts, particularly the internal organs, contain high concentrations of one of the most powerful toxins found in nature, tetrodotoxin (which takes its name from the Tetraodontiformes). This alkaloid, which is up to 1200 times more potent than cyanide and has no known antidote, blocks action potentials in nerve cells by binding to voltage-gated sodium channels, thus causing motor paralysis and ultimately death from suffocation within minutes. It is found in several pufferfish genera and sometimes associated with bright colours and distinct markings, thus probably representing one of numerous examples of aposematism. TetrodotoxinInterestingly, tetrodotoxin is not produced by the fish themselves but by endogenous bacteria (e.g. species in the genera Vibrio and Pseudomonas), which are ingested with food. The mechanism by which the fish avoid self-poisoning revolves around a fascinating story of molecular convergence. Tetrodotoxin resistance is achieved by amino acid changes in all eight types of sodium channel, which substantially reduce affinity to the toxin. Intriguingly, these changes evolved independently in four phylogenetically diverse pufferfish species, but involve only very few sites, suggesting that selection for normal channel function strongly limits the possibilities for resistance-conveying mutations. Tetrodotoxin resistance thus represents “an example of natural selection acting upon a complete gene family, repeatedly arriving at a diverse but limited number of adaptive changes within the same genome” (Jost et al. 2008, Molecular Biology and Evolution, vol. 25, pp. 1016-1024).

Tetrodotoxin is found in many other organisms

Blue-ringed octopusThe employment of tetrodotoxin as a defence (or sometimes predatory venom) is rampantly convergent, remarkably including marine as well as non-marine organisms. In the marine realm, it has so far been isolated from another fish (the marine goby Yongeichthys criniger), marine worms of different phyla (flatworms, ribbon worms, arrow worms and annelids), blue-ringed octopuses (genus Hapalochlaena), various genera of marine snails, crustaceans (the horseshoe crab Carcinoscorpius rotundicauda as well as xanthid crabs from different genera) and starfish (genus Astropecten). Beyond the oceans, the toxin is found in a wide range of amphibians from different families, particularly newts in the genus Taricha and frogs in the genus Atelopus. As it seems likely that their tetrodotoxin is also of bacterial origin, the symbiosis between tetrodotoxin-producing bacteria and animals, as well as the resistance of these animals to the toxin, has probably evolved independently several times. Interestingly, some predators of these poisonous animals might have convergently acquired tetrodotoxin resistance. Garter snakes (Thamnophis sirtalis) that prey on California newts (Taricha torosa) can eat them without any harm done, whereas garter snake populations that do not encounter the newts in the wild are poisoned when fed newts in the laboratory.

Read more about convergent evolution of tetrodotoxin at the Map of Life. You’ll find plenty of interesting convergences relating to pufferfish too: amazingly, they aren’t the only fish that can puff themselves up like a spiky football to scare away would-be predators!


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