Similar Venom Found in Two Species

Reptiles and mammals may represent different classes in the animal kingdom, but researchers in the Department of Organismic and Evolutionary Biology have found that similar molecular changes cause both a lizard and a shrew to produce a toxin—a discovery that may shed light on similar changes that occur in other animals.

“Our big picture question was how do proteins evolve new functions? How do you go from a harmless digestive enzyme into something that’s a toxin?” said Hopi Hoekstra, an associate professor of natural sciences and one of the authors of the study. “We were particularly interested in the molecular changes that supercharge the enzyme.”

Shrews, along with platypuses, are among the few venomous mammals, and they produce a toxin in modified salivary glands that enters their prey’s circulatory system when they bite, Hoekstra explained.

The toxin is an enzyme, a type of protein that accelerates the rate of chemical reactions by bringing reactants together in the enzyme’s active site.

When lead author Yael T. Aminetzach, a postdoctoral fellow in OEB, compared the toxin to a nontoxic counterpart, she found that the molecular changes occurred in active site of the enzyme. While the toxins from the lizard and the shrew are distinct, the overall trend of changes turned out to be the same.

“There were three very important changes that can potentially increase the catalytic ability of the enzyme,” said Aminetzach. “The active site opened up, the loops around the active site became more flexible, and the surface electrostatic charge changed from negative to positive.”

These general changes may help to better guide the substrates into the active site of the enzyme.

Aminetzach said this week that she hopes to continue with this research and collect data on other snakes and lizards to see whether similar changes in the active site of other enzymes also led to the enzymes eventually evolving into toxins.

Hoekstra added that they also want to learn which of the changes actually cause the protein to become toxic.

“Our long term goal is to reconstruct the protein mutation by mutation and see if all of the amino acid changes are really necessary,” Hoekstra said.

—Staff writer Alissa M. D’Gama can be reached at adgama@fas.harvard.edu.