Adaptive evolution of tetrodotoxin resistance in animals.

Tetrodotoxin (TTX), first isolated from pufferfish (tetraodontids), is a highly potent neurotoxin that selectively binds to voltage-gated sodium channels (Na(v)) in muscle and nerve tissues causing paralysis and death. Saxitoxin (STX) is a TTX-related neurotoxin produced by dinoflagellates. Recent investigations have implicated diverse substitutions in the P-loop regions of skeletal muscle and neuronal Na(v) channels in the convergent evolution of neurotoxin resistance in pufferfish, garter snakes and softshell clams, which has enabled them to feed on TTX- and STX-bearing organisms.