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  The Straits Times 22 Nov 05
Pufferfish toxin mystery: S'pore team finds the key
 by Chang Ai-Lien

THE deadly pufferfish (above) not only feeds on poison, but the poison actually helps it to breed.

The tetrodotoxin found in its skin and organs is 20 times deadlier than cyanide, yet this is what it needs for food, protection and reproduction.

Scientists here have pinpointed an evolutionary adaptation at a genetic level that has made the fish immune to the poison. In fact, it was a change of a single pair of chemical letters - out of a total of 400 million in its genetic makeup - which is responsible for its resilience.

The findings could point the way to new medical treatments. 'It will help us understand how the toxin works, and how we can create an antidote,' said Associate Professor Byrappa Venkatesh of the Institute of Molecular and Cell Biology (IMCB), who led the research team.

Tetrodotoxin causes paralysis of the muscles and nerves, and death through respiratory failure. However, the potent toxin has also been found to be an extremely powerful painkiller, when administered in tiny, non-lethal doses. So it may prove a boon for people such as cancer patients and drug addicts going through withdrawal symptoms. It is currently being tested in China.

There are 120 species of pufferfish, and they all have this powerful poison which is not neutralised by cooking. They have no known predators in nature because of their toxin - except humans. Specially trained chefs know how to remove the poison before serving the dish. Nonetheless, several people die each year from eating improperly prepared pufferfish, since varieties such as fugu are considered a delicacy in Japan and South Korea.

By comparing the genome sequences of pufferfish, zebrafish and man, the research team was able to pinpoint the evolutionary adaptation that enabled the fish to become resistant to the poison.

There have been only a few instances in which such an adaptation has been traced to changes at the DNA level, said Prof Venkatesh. The scientists believe, besides helping to remove pufferfish from predators' menus, its resistance to tetrodotoxin means it can consume food that contains the poison, which other fish avoid.

Pufferfish do not produce the toxin on their own. It comes from marine bacteria. The fish accumulate it by feeding on contaminated marine life near the seabed - including crabs, shells and starfish. Female pufferfish also use tetrodotoxin as a pheromone to attract males during spawning.

The work by the IMCB and the National University of Singapore has been published in the prestigious journal Current Biology. The IMCB team behind the discovery was a key player in an international consortium that sequenced the fugu genome in 2002.

By comparing genome sequences of fugu and humans, scientists have been able to discover new genes and gene regulatory elements in the human genome.
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