Shrew Digestive Enzyme Repurposed into Venom

The diminutive short-tailed shrew (Blarina brevicauda) has long been known to possess toxic saliva. Early reports indicated that humans bitten by short-tailed shrews suffered swelling and burning sensations in the region surrounding the bite. While not lethal to humans, the venom is apparently lethal to the shrew’s main prey (insects, frogs, mice and other small vertebrates). Thus, short-tailed shrews use their venom to subdue prey larger than themselves.

blarina
Figure 1. A short-tailed shrew (Blarina brevicauda) searching for food. (Photo by Gilles Gonthier).

Short-tailed shrews are not the only venomous soricomorphs; the
Haitian solenodon (Solenodon paradoxus), the European water shrew (Neomys fodiens), and the Mediterranean shrew (Neomys anomalous) also produce toxic saliva. These venoms are produced in salivary glands near the front of the mouth and enter the victim’s bloodstream when it is bitten.

In 2004, Kita and colleagues isolated and characterized the toxin used by short-tailed shrews, called blarina toxin (BLTX). When the purified toxin was injected into mice, their breathing became erratic, paralysis and convulsions ensued, and the mice eventually died. Evidently, the blarina toxin degrades relatively quickly once injected, which may explain why the short-tailed shrews are not affected when they eat their prey. These authors also noted that the BLTX toxin was similar to lizard venom.

Following on the heels of the 2004 research, Aminetzach and colleagues (2009) demonstrated how this novel shrew toxin evolved. BLTX turns out to be very similar to a digestive enzyme called
kallikrein. Apperently, a series of molecular changes in the gene for the digestive enzyme led to the formation of a novel toxic protein in shrews. These mutations changed the active site and the rate of enzyme action such that it BLTX produces large quantities of bradykinin, its catalytic product. When a shrew bites its prey, the BLTX in its saliva enters the victim’s circulation. Here BLTX acts to catalyze a reaction that generates bradykinin. Because BLTX greatly accelerates this reaction, the victim’s circulatory system is quickly swamped with bradykinin, leading to paralysis and death.

Interestingly, comparisons of blarina toxin (BLTX) with the venom (GTX) of the
Mexican beaded lizard (Heloderma horridum) show some remarkable functional similarities. Aminetzach and colleagues (2009) suggest that similar digestive enzymes were repurposed through convergent evolution in their molecular structure into novel venoms at least twice during the evolution of terrestrial vertebrates, once in some reptiles and again independently in a few mammals.

References

Aminetzach, Y.T., Srouji, J.R., Kong, C.Y., and H.E. Hoekstra. 2009. Convergent evolution of novel protein function in shrew and lizard venom. Current Biology, 19:1-7.

Kita, M., Nakamura, Y., Okumura, Y., Ohdachi, S.D., Oba, Y., Yoshikuni, M., Kido, H., and D. Uemura. 2004. Blarina toxin, a mammalian lethal venom from the short-tailed shrew Blarina brevicauda: Isolation and characterization. Proceedings of the National Academy of Sciences. 101: 7542-7547.