Evolution of an Arsenal

Fry, Bryan G.; Scheib, Holger; Weerd, Louise van der; Young, Bruce A.; McNaughtan, J; Ramjan, S. F. Ryan; Vidal, Nicolás; Poelmann, Robert E.; Norman, Janette A

doi:10.1074/mcp.m700094-mcp200

Cited by 313 publications

(176 citation statements)

References 58 publications

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“…Separate ducts were shown to lead from each compartment, opening between successive serrated pleurodont teeth (Fig. 2B), making this the most structurally complex reptile venom gland described to date (9)(10)(11). Consistent with the positioning of the ducts, the teeth lack the grooves commonly associated with venom delivery in helodermatid lizards (Fig.…”

Section: Resultsmentioning

confidence: 99%

A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus ( Megalania ) priscus

Fry

Wroe

Teeuwisse³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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130

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The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus. We find that the lightweight skull is relatively poorly adapted to generate high bite forces but better adapted to resist high pulling loads. We reject the popular notion regarding toxic bacteria utilization. Instead, we demonstrate that the effects of deep wounds inflicted are potentiated through venom with toxic activities including anticoagulation and shock induction. Anatomical comparisons of V. komodoensis with V. (Megalania) priscus fossils suggest that the closely related extinct giant was the largest venomous animal to have ever lived. evolution ͉ phylogeny ͉ squamate ͉ protein ͉ toxin P redation by Varanus komodoensis, the world's largest extant lizard, has been an area of great controversy (cf. ref. 1). Three-dimensional finite element (FE) modeling has suggested that the skull and bite force of V. komodoensis are weak (2). However, the relevance of bite force and cranial mechanics to interpretations of feeding behavior cannot be fully evaluated in the absence of comparative data. Moreover, this previous analysis did not account for gape angle, which can significantly influence results (3). Irrespective of evidence for or against a powerful bite, V. komodoensis is clearly capable of opening wounds that can lead to death through blood loss (4). Controversially, the proposition that utilization of pathogenic bacteria facilitates the prey capture (4, 5) has been widely accepted despite a conspicuous lack of supporting evidence for a role in predation. In contrast, recent evidence has revealed that venom is a basal characteristic of the Toxicofera reptile clade (6), which includes the varanid lizards (7), suggesting a potential role of venom in prey capture by V. komodoensis that has remained unexplored. This is consistent with prey animals reported as being unusually quiet after being bitten and rapidly going into shock (4) and the anecdotal reports of persistent bleeding in human victims after bites (including B.G.F.'s personal observations). Shock-inducing and prolonged bleeding pathophysiological effects are also characteristic of helodermatid lizard envenomations (cf. ref . 8), consistent with the similarity between helodermatid and varanid venoms (6).Here, we examine the feeding ecology of V. komodoensis in detail. We compare the skull architecture and dentition with the related extinct giant V. priscus (Megalania). In this 3D finite element modeling of reptilian cranial mechanics that applies a comparative approach, we also compare the bite force and skull stress performance with that of Crocodylus porosus (Australian Saltwater Crocodile), including the identification of optimal gape angle (an aspect not considered in previous nonreptilian comparative FE analyses). We als...

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Section: Resultsmentioning

confidence: 99%

A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus ( Megalania ) priscus

Fry

Wroe

Teeuwisse³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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130

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“…Hyaluronidase is found in the venom of toxicoferan reptiles [with isoforms sequences generated in the case of snakes (55,65) and helodermatid lizards (Fry et al, unpublished results; Genbank accession number EU790961)], stonefish (110), and hymenopterans (61,77) (Figure 3). In addition to venoms for which protein sequences have been obtained, hyaluronidase activity has been reported in octopus (147), spider (107), and scorpion venoms (15), but the corresponding enzymes have not yet been sequenced.…”

Section: Hyaluronidasementioning

confidence: 99%

“…Kunitz-scaffold toxins have been found in the venoms of snakes (55,66), sea anemones (10,17,69,101), the solitary wasp Anopilus samariensis (68), the scorpion Hadrurus gertschi (139), the polychaete worm Sabellastarte magnifica (UniProt accession number P84875), the snail Conus stratius (16), and the gorgonian coral Melithaea caledonica (UniProt accession number P82968). This peptide has also been recruited twice into spider venoms; the scaffold-type in the araneamorph spider Araneus ventricosus is phylogenetically distinct from that characterized from the mygalomorph Ornithoctonus huwena (Figure 4).…”

Section: Kunitz-type Peptidesmentioning

confidence: 99%

“…In contrast, snakes possess highly developed but non-compartmentalized maxillary venom glands with developmentally suppressed mandibular glands. Spread across the advanced snakes is an enormous variation of fang and venom gland morphologies (55) that arose from the ancient serpent dental uncoupling (156). Further, within the advanced snakes, divergence has resulted in four derived lineages [twice within the Lamprophiidae family (Atractaspis and Homoroselaps genera), and once each at the base of the Elapidae and Viperidae families] that possess intricate hollow-front, fanged, and high-pressure delivery systems (55).…”

Section: Introductionmentioning

confidence: 99%

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The Toxicogenomic Multiverse: Convergent Recruitment of Proteins Into Animal Venoms

Fry

Roelants

Champagne

et al. 2009

Annu. Rev. Genom. Hum. Genet.

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722

778

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Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have included AVIT/colipase/prokineticin, CAP, chitinase, cystatin, defensins, hyaluronidase, Kunitz, lectin, lipocalin, natriuretic peptide, peptidase S1, phospholipase A 2 , sphingomyelinase D, and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of invertebrates (e.g., fleas, leeches, kissing bugs, mosquitoes, and ticks) and vertebrates (e.g., vampire bats). Here, we discuss a number of overarching structural, functional, and evolutionary generalities of the protein families from which these toxins have been frequently recruited and propose a revised and expanded working definition for venom. Given the large number of striking similarities between the protein compositions of conventional venoms and hematophagous secretions, we argue that the latter should also fall under the same definition. 483

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“…Polymorphisms at a much larger genomic scale, such as gene duplications and deletions (Stranger et al 2007), also can alter the expression level of a particular protein (Nguyen et al 2006). The correlation between gene copy-number differences and changes in gene expression has been documented previously (Cheng et al 2005;Freeman et al 2006;Nair et al 2008), including in venoms (Margres et al 2015b), and venom protein families are believed to be the result of gene duplication and positive selection (Casewell et al 2011) via the birth-anddeath model of protein evolution (Fry et al 2008). The significant expression variation we detected therefore could be the result of variation in copy number, assuming that variation in copy number would affect low-expression (and presumably low-copy) genes more than high-expression, high-copy genes (e.g., the difference between 10 and 12 copies for a particular protein may not be significant, but the difference between 2 and 4 copies may be).…”

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confidence: 99%

Expression Differentiation Is Constrained to Low-Expression Proteins over Ecological Timescales

Margres¹,

Wray²,

Seavy³

et al. 2015

Genetics

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Protein expression level is one of the strongest predictors of protein sequence evolutionary rate, with high-expression protein sequences evolving at slower rates than low-expression protein sequences largely because of constraints on protein folding and function. Expression evolutionary rates also have been shown to be negatively correlated with expression level across human and mouse orthologs over relatively long divergence times (i.e., 100 million years). Long-term evolutionary patterns, however, often cannot be extrapolated to microevolutionary processes (and vice versa), and whether this relationship holds for traits evolving under directional selection within a single species over ecological timescales (i.e., ,5000 years) is unknown and not necessarily expected. Expression is a metabolically costly process, and the expression level of a particular protein is predicted to be a tradeoff between the benefit of its function and the costs of its expression. Selection should drive the expression level of all proteins close to values that maximize fitness, particularly for high-expression proteins because of the increased energetic cost of production. Therefore, stabilizing selection may reduce the amount of standing expression variation for high-expression proteins, and in combination with physiological constraints that may place an upper bound on the range of beneficial expression variation, these constraints could severely limit the availability of beneficial expression variants. To determine whether rapid-expression evolution was restricted to low-expression proteins owing to these constraints on highly expressed proteins over ecological timescales, we compared venom protein expression levels across mainland and island populations for three species of pit vipers. We detected significant differentiation in protein expression levels in two of the three species and found that rapid-expression differentiation was restricted to low-expression proteins. Our results suggest that various constraints on high-expression proteins reduce the availability of beneficial expression variants relative to lowexpression proteins, enabling low-expression proteins to evolve and potentially lead to more rapid adaptation.KEYWORDS protein expression; selective constraints; evolutionary rates; adaptation T HE expression level of a protein is one of the strongest predictors of protein sequence evolutionary rate; sequences of highly expressed proteins evolve more slowly than low-expression proteins (Duret and Mouchiroud 1999;Pal et al. 2001;Gout et al. 2010;Yang et al. 2012;Nabholz et al. 2013;Park et al. 2013). This relationship may be a function of specific selective constraints on sequences to avoid protein misfolding (Drummond et al. 2005;Geiler-Samerotte et al. 2011), protein misinteractions (Yang et al. 2012, a decrease in protein function (Cherry 2010;Gout et al. 2010), and/or messenger RNA (mRNA) misfolding (Park et al. 2013). Analyses of microarray data have shown that expression evolutionary rate is also negatively...

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Evolution of an Arsenal

Cited by 313 publications

References 58 publications

A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus ( Megalania ) priscus

A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus ( Megalania ) priscus

The Toxicogenomic Multiverse: Convergent Recruitment of Proteins Into Animal Venoms

Expression Differentiation Is Constrained to Low-Expression Proteins over Ecological Timescales

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