BioEd Online

When snakes evolved venom, they co-opted proteins from all over their bodies, says an analysis of 24 different toxins. Surprisingly, very tiny tweaks were enough to transform harmless proteins into deadly poison, and this may help drug designers to create proteins with precise biological effects.

Venomous snakes developed glands for the storage and dispersal of their saliva about 60-70 million years ago. Since then, various species have built up an arsenal of toxins to attack their victims.

Different venoms attack different types of cell in the body, for example muscle cells or blood cells. This dramatic specificity has led scientists to speculate that the venoms originate from proteins produced in different organs throughout the body, which already interact with these cell types. But champions of this theory lacked hard evidence from more than a few toxins.

Poison puzzle

The puzzle attracted the attention of Bryan Fry of the Australian Venom Research Unit within the University of Melbourne in Parkville, Victoria. He embarked on a complex genetic analysis of the 24 types of known snake toxins.

This involved comparing the amino-acid sequences of the toxins with those of proteins from the brain, heart, liver and other organs. He found that 21 of the 24 venom proteins seemed to be related to proteins from these parts of the body.

"This highlights the tremendous diversity of snake-venom toxins," says venom expert Wolfgang Wüster of the University of Wales, Bangor, UK. "What he's shown here is that they come from all over the shop."

Surprisingly, very small adjustments of the sequence were enough to create the toxic forms.

"Despite the incredible changes in bioactivity that occur, the basic molecular scaffold and three-dimensional shape doesn't change notably," Fry says. The results of his analysis appear this week in Genome Research¹.

Fry believes that a close examination of the molecular make-up of toxins and the changes that have affected their function so dramatically will help drug developers to work backwards and understand how normal proteins work.

He is continuing his research to understand how snakes' venom glands first started using the proteins.