Mexican beaded lizard shares venom source with shrew

Mexican Beaded Lizard (Heloderma horridum)

North American short-tailed shrew (Blarina brevicaudis) Photo: Gilles Gonthier

"It's remarkable that the same types of changes have independently promoted the same toxic end product," says one of the study's authors, Hopi E. Hoekstra, a professor in Harvard's Department of Organismic and Evolutionary Biology.

"The venom is essentially an overactivation of the original digestive enzyme, amplifying its effects," says co-author Yael T. Aminetzach, a postdoctoral researcher in the same department. "What had been a mild anticoagulant in the salivary glands of both species has become a much more extreme compound that causes paralysis and death in prey that is bitten."

In the one part of the study, Aminetzach and her colleagues compared a toxin found in the salivary glands of the insectivorous North American short-tailed shrew Blarina brevicauda to a similar digestive enzyme, kallikrein.

They found that the molecular differences between kallikrein and its toxic descendent are localized around the enzyme's active site.

"Catalysis is fostered by three specific changes that increase enzyme activity," Aminetzach says. "The active site is physically opened up, and the loops surrounding it become more flexible. The area around the active site also becomes positively charged, serving to better guide the substrate directly into the active site."

The researchers also explored the evolution of another kallikreinlike toxin in the Mexican beaded lizard (Heloderma horridum), one of two venomous lizards known, the other being the Gila monster (Heloderma suspectum). They found that this toxin, while distinct from the shrew toxin, nonetheless shows the same catalytic enhancement relative to the kallikrein enzyme.

They found the lizard toxin, too, could be produced from kallikrein via molecular modifications similar to those producing the shrew toxin. So in both cases, the harmless digestive enzyme kallikrein seems to have evolved into a deadly venom.

This raises an important question for future research -- If a North American short-tailed shrew were placed in a cage with a Mexican beaded lizard, who would win?