The discovery is reported in the April 7 issue of the journal Nature. The authors suggest that it has wide ranging implications for the evolution of shellfish in the presence of toxic algae and increases the risk of PSP to people who eat clams by enabling contaminated clams to survive in the presence of toxins.
The report, "Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP," was written by a team of scientists, including Laurie Connell of the University of Maine School of Marine Sciences. It describes differences in the responses of two soft shell clam populations -- one in the Bay of Fundy and the other in the Lawrencetown estuary in Nova Scotia -- to saxitoxin as well as tetrodotoxin, a powerful toxin derived from the puffer fish.
The lead author is V. Monica Bricelj of the Institute for Marine Biosciences in Halifax, Nova Scotia, and in addition to Connell, co-authors are Keiichi Konoki, Todd Scheuer, and William A. Catterall of the University of Washington; Scott P. MacQuarrie of the Institute for Marine Biosciences; and Vera L. Trainer of the National Oceanic and Atmospheric Administration in Seattle.
"Since the 1960s, it's been known that different species of shellfish have different resistance to PSP toxins," says Connell. "This is the first time the source of that resistance has been shown. We now have a marker that can be used to determine if clams have this mutation. It's easy to use and could help reduce the time of clam flat closures (related to red tide)."
Betty Twarog, a neurophysiologist who works at UMaine's Darling Marine Center in Walp ole, Maine, did research in the 1960s and 1970s showing that PSP toxin resistance varies among shellfish species.
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.