In laboratory studies, the investigators exposed clams to PSP toxins and monitored the shellfish for mortality and potentially harmful changes in burrowing behavior. They found that clams that came from areas with a history of red tides had less sensitivity to the toxins than did clams from an area with no such history. They showed that nerves taken from the two clam populations also function differently, with those from exposed the population showing markedly less sensitivity to the toxins.
Tracking these differences down to the genomic level and comparing DNA sequences from the two populations enabled Connell to identify the single nucleotide mutation that corresponded with toxin resistance. She showed that the mutation changed an amino acid in a channel, a protein in the nerve cell membrane that allows sodium ions to pass through the membrane. Regulation of sodium is critical to nerve cell function. Without the mutation, the PSP toxins can bind to the sodium channel, shutting down the nerve and leading to paralysis.
The toxin acts like a cork in a bottle, preventing sodium ions from flowing through the membrane, says Connell. The mutation prevents the cork from sticking.
"This is a very conservative mutation in the protein. It was thought that the sodium channel was flexible at this location. We've shown that it is not, that it is rigid," says Connell. That could have implications for medical research, she notes, leading to new drugs for treatment of neuromuscular disease.
Because clams that possess the mutation are more likely to survive in red tide contaminated areas, the toxin and the mutation act together to influence the shellfish population, the authors conclude.