Convergent Evolution of Novel Protein Function in Shrew and Lizard Venom

Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
Current biology: CB (Impact Factor: 9.57). 10/2009; 19(22):1925-31. DOI: 10.1016/j.cub.2009.09.022
Source: PubMed


How do proteins evolve novel functions? To address this question, we are studying the evolution of a mammalian toxin, the serine protease BLTX [1], from the salivary glands of the North American shrew Blarina brevicauda. Here, we examine the molecular changes responsible for promoting BLTX toxicity. First, we show that regulatory loops surrounding the BLTX active site have evolved adaptively via acquisition of small insertions and subsequent accelerated sequence evolution. Second, these mutations introduce a novel chemical environment into the catalytic cleft of BLTX. Third, molecular-dynamic simulations show that the observed changes create a novel chemical and physical topology consistent with increased enzyme catalysis. Finally, we show that a toxic serine protease from the Mexican beaded lizard (GTX) [2] has evolved convergently through almost identical functional changes. Together, these results suggest that the evolution of toxicity might be predictable-arising via adaptive structural modification of analogous labile regulatory loops of an ancestral serine protease-and thus might aid in the identification of other toxic proteins.

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    • "Several of the remipede PS1 sequences contain short insertions within the region encompassed by the catalytic triad. Interestingly, insertions found in this region of kallikrein-type PS1s expressed in the salivary glands of the shrew Blarina brevicauda have been hypothesized to be associated with possibly enhancing enzymatic activity (Aminetzach et al. 2009). A similar insertion reported from a kallikrein toxin expressed in the venom glands of the Gila monster (Heloderma horridum), however, was subsequently found to be a sequencing artifact (Fry et al. 2010). "
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    • "Interestingly, as Fry et al. (2009a,b, 2012) are aware, there is a well-established structural and functional link between several venom toxins of B. brevicauda and that of the venomous helodermatid lizards, the Gila monster (Heloderma suspectum), and beaded lizard (Heloderma horridum; Kita et al., 2004; Ligabue-Braun et al., 2012). In particular, blarina toxin from B. brevicauda venom and gilatoxin from H. suspectum venom, both appear to be structurally similar toxic kallikreins that are derived from non-toxic kallikrein precursors, an example of convergent evolution (Aminetzach et al., 2009) involving recruitment of specialized serine proteases. We mention this very interesting example of functional evolutionary convergence in order to reinforce that closely similar toxins may develop in divergent animals, and the knowledge of how these are used is central in assigning terminology that reflects their respective function (s). "

    Full-text · Article · Nov 2012 · Toxicon
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    • "Changes in different processes imply that natural selection can act on multiple developmental processes to achieve the same outcomes , whereas changes in the same processes may suggest that natural selection is constrained to act on one developmental event (Losos, 2011; Sanger et al., 2012). In recent years, several examples of convergent evolution at the molecular, cellular and morphological levels have been examined (Aminetzach et al., 2009; Moczek et al., 2006; Protas et al., 2006; Sucena et al., 2003; Tanaka et al., 2009; Wittkopp et al., 2003). "
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