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.


Available from: Hopi E Hoekstra
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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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    ABSTRACT: Animal venoms have evolved many times. Venomous species are especially common in three of the four main groups of arthropods (Chelicerata, Myriapoda, Hexapoda), which together represent tens of thousands of species of venomous spiders, scorpions, centipedes and hymenopterans. Surprisingly, despite their great diversity of body plans there is no unambiguous evidence that any crustacean is venomous. We provide the first conclusive evidence that the aquatic, blind and cave-dwelling remipede crustaceans are venomous, and that venoms evolved in all four major arthropod groups. We produced a three-dimensional reconstruction of the venom delivery apparatus of the remipede Speleonectes tulumensis, showing that remipedes can inject venom in a controlled manner. A transcriptomic profile of its venom glands shows that they express a unique cocktail of transcripts coding for known venom toxins, including a diversity of enzymes and a probable paralytic neurotoxin very similar to one described from spider venom. We screened a transcriptomic library obtained from whole animals and identified a non-toxin paralogue of the remipede neurotoxin that is not expressed in the venom glands. This allowed us to reconstruct its probable evolutionary origin, and underlines the importance of incorporating data derived from non-venom gland tissue to elucidate the evolution of candidate venom proteins. This first glimpse into the venom of a crustacean and primitively aquatic arthropod reveals conspicuous differences from the venoms of other predatory arthropods such as centipedes, scorpions and spiders, and contributes valuable information for ultimately disentangling the many factors shaping the biology and evolution of venoms and venomous species.
    Molecular Biology and Evolution 10/2013; 31(1). DOI:10.1093/molbev/mst199 · 9.11 Impact Factor
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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). "

    Toxicon 11/2012; 64. DOI:10.1016/j.toxicon.2012.11.005 · 2.49 Impact Factor
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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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    ABSTRACT: Convergent morphologies often arise due to similar selective pressures in independent lineages. It is poorly understood whether the same or different developmental genetic mechanisms underlie such convergence. Here we show that independent evolution of a reproductive trait, ovariole number, has resulted from changes in distinct developmental mechanisms, each of which may have a different underlying genetic basis in Drosophila. Ovariole number in Drosophila is species-specific, highly variable, and largely under genetic control. Convergent changes in Drosophila ovariole number have evolved independently within and between species. We previously showed that the number of a specific ovarian cell type, terminal filament (TF) cells, determines ovariole number. Here we examine TF cell development in different Drosophila lineages that independently evolved a significantly lower ovariole number than the D. melanogaster Oregon R strain. We show that in these Drosophila lineages, reduction in ovariole number occurs primarily through variations in one of two different developmental mechanisms: (1) reduced number of somatic gonad precursors (SGP cells) specified during embryogenesis; or (2) alterations of somatic gonad cell morphogenesis and differentiation in larval life. Mutations in the D. melanogaster Insulin Receptor (InR) alter SGP cell number but not ovarian morphogenesis, while targeted loss of function of bric-à-brac 2 (bab2) affects morphogenesis without changing SGP cell number. Thus, evolution can produce similar ovariole numbers through distinct developmental mechanisms, likely controlled by different genetic mechanisms.
    Developmental Biology 09/2012; 372(1):120-30. DOI:10.1016/j.ydbio.2012.09.014 · 3.55 Impact Factor
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