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Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails.

Dutertre S, Jin AH, Vetter I, Hamilton B, Sunagar K, Lavergne V, Dutertre V, Fry BG, Antunes A, Venter DJ, Alewood PF, Lewis RJ - Nat Commun (2014)

Bottom Line: Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans.Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms.We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072 Queensland, Australia [2] Institut des Biomolécules Max Mousseron, UMR 5247, Université Montpellier 2-CNRS, Place Eugène Bataillon, Montpellier Cedex 5 34095, France.

ABSTRACT
Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans. In contrast, C. geographus predation-evoked venom contains prey-specific toxins mostly inactive at human targets. Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms. A specialized defensive envenomation strategy is widely evolved across worm, mollusk and fish-hunting cone snails. We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets.

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Distribution of toxins in C. geographus venom duct and proposed mechanism for venom release.(a) Twelve venom gland sections were spotted on a MALDI plate together with predation- and defence-evoked venom (O, oesophagus; P, proboscis; RS, radular sac; SG, salivary gland). (b) The resulting averaged spectrum is highly complex in the range 1,000–4,000 kDa corresponding to the size of most conotoxins (10–30 amino acids). (c) Gel view representation of MALDI results reveals distinct regionalization of many venom components along the duct. For example, the predatory toxin at 3,175 kDa and defensive toxin at 1,417 kDa show clear non-overlapping distribution along the duct. (d) Quantification of five major predatory (including conopressin-G at 1,035 kDa) and defensive (including α-GII at 1,417 kDa, μ-GIIIA at 2,610 kDa and ω-GVIIA at 3,316 kDa) toxins confirms this region-specific toxin production. (e) Histology (formaldehyde-fixed animal embedded in paraffin) reveals structural heterogeneity along the venom duct, including regions with a dense layer of secretory cells and a small lumen and others with a looser cell arrangement and a larger lumen, which could support such regional specialization. Gomori’s Trichrome stain shows muscle fibres in red, collagen in green and nuclei in blue/black (scale bar, 20 μm). (f) A simple hypothesis to explain the generation of separate stimulus-evoked venoms is proposed. An initial stimulus (predatory or defensive) is perceived by mechanical, visual and/or chemical (olfactory) sensors that transmit information to the cerebral ganglia surrounding the oesophagus (O) to activate two separate neuronal circuits. Predation-evoked stimuli activate neuronal circuit (blue) innervating the distal venom duct, causing the release of predatory venom peptides into the venom duct lumen. Similarly, threats including larger fish and cephalopods activate a separate defensive neuronal circuit (green) that innervates the proximal venom duct, causing the release of defensive toxins into the lumen. These lumen contents are then moved to the proboscis by a synchronized contraction of the muscular venom bulb to generate the injected ‘predation-evoked’ and ‘defence-evoked’ venoms. This key role of the venom bulb allows the rapid switch between the predation- and defence-evoked venoms observed. This mechanism of stimulus-dependent release of toxins from different sections of the venom duct explains how distinct predation- and defence-evoked venoms are generated.
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f3: Distribution of toxins in C. geographus venom duct and proposed mechanism for venom release.(a) Twelve venom gland sections were spotted on a MALDI plate together with predation- and defence-evoked venom (O, oesophagus; P, proboscis; RS, radular sac; SG, salivary gland). (b) The resulting averaged spectrum is highly complex in the range 1,000–4,000 kDa corresponding to the size of most conotoxins (10–30 amino acids). (c) Gel view representation of MALDI results reveals distinct regionalization of many venom components along the duct. For example, the predatory toxin at 3,175 kDa and defensive toxin at 1,417 kDa show clear non-overlapping distribution along the duct. (d) Quantification of five major predatory (including conopressin-G at 1,035 kDa) and defensive (including α-GII at 1,417 kDa, μ-GIIIA at 2,610 kDa and ω-GVIIA at 3,316 kDa) toxins confirms this region-specific toxin production. (e) Histology (formaldehyde-fixed animal embedded in paraffin) reveals structural heterogeneity along the venom duct, including regions with a dense layer of secretory cells and a small lumen and others with a looser cell arrangement and a larger lumen, which could support such regional specialization. Gomori’s Trichrome stain shows muscle fibres in red, collagen in green and nuclei in blue/black (scale bar, 20 μm). (f) A simple hypothesis to explain the generation of separate stimulus-evoked venoms is proposed. An initial stimulus (predatory or defensive) is perceived by mechanical, visual and/or chemical (olfactory) sensors that transmit information to the cerebral ganglia surrounding the oesophagus (O) to activate two separate neuronal circuits. Predation-evoked stimuli activate neuronal circuit (blue) innervating the distal venom duct, causing the release of predatory venom peptides into the venom duct lumen. Similarly, threats including larger fish and cephalopods activate a separate defensive neuronal circuit (green) that innervates the proximal venom duct, causing the release of defensive toxins into the lumen. These lumen contents are then moved to the proboscis by a synchronized contraction of the muscular venom bulb to generate the injected ‘predation-evoked’ and ‘defence-evoked’ venoms. This key role of the venom bulb allows the rapid switch between the predation- and defence-evoked venoms observed. This mechanism of stimulus-dependent release of toxins from different sections of the venom duct explains how distinct predation- and defence-evoked venoms are generated.

Mentions: The long, convoluted venom duct is the dominant toxin secretory organ in cone snails, but it is unclear if other embryologically related organs might also participate in venom production12. Analyses of the transcriptomes and proteomes of the interconnected venom gland, salivary gland and radular sac of C. geographus unequivocally demonstrated that both predation- and defence-evoked venoms arise from the venom duct and not these other associated tissues (Supplementary Figs 12 and 13), with 127 conotoxin sequences recovered from the venom duct, including 43 confirmed by tandem mass spectrometry (MS/MS) (Supplementary Table 1). In contrast, no conotoxin sequences were found in the salivary gland, and only three rare conotoxin transcripts were identified in the radula sac transcriptome, although these were not detected in the injected venoms. To understand how a single gland can rapidly and reversibly produce two distinct venoms, we analysed the venom peptide composition along the venom duct of C. geographus (Fig. 3a–c). Unexpectedly, the paralytic toxins found in the defence-evoked venom were abundant in the proximal duct (sections 7–12), whereas the major toxins found in the predation-evoked venom dominated the distal sections (sections 1–6 close to the pharynx) (Fig. 3d, Supplementary Fig. 14). In addition, structural differences within the venom duct support the distinct partition of the gland producing toxins (Fig. 3e). These results suggest that stimulus-dependent spatiotemporal release of toxins from different segments of the venom duct can generate functionally and biochemically distinct predation- and defence-evoked venoms (Fig. 3f).


Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails.

Dutertre S, Jin AH, Vetter I, Hamilton B, Sunagar K, Lavergne V, Dutertre V, Fry BG, Antunes A, Venter DJ, Alewood PF, Lewis RJ - Nat Commun (2014)

Distribution of toxins in C. geographus venom duct and proposed mechanism for venom release.(a) Twelve venom gland sections were spotted on a MALDI plate together with predation- and defence-evoked venom (O, oesophagus; P, proboscis; RS, radular sac; SG, salivary gland). (b) The resulting averaged spectrum is highly complex in the range 1,000–4,000 kDa corresponding to the size of most conotoxins (10–30 amino acids). (c) Gel view representation of MALDI results reveals distinct regionalization of many venom components along the duct. For example, the predatory toxin at 3,175 kDa and defensive toxin at 1,417 kDa show clear non-overlapping distribution along the duct. (d) Quantification of five major predatory (including conopressin-G at 1,035 kDa) and defensive (including α-GII at 1,417 kDa, μ-GIIIA at 2,610 kDa and ω-GVIIA at 3,316 kDa) toxins confirms this region-specific toxin production. (e) Histology (formaldehyde-fixed animal embedded in paraffin) reveals structural heterogeneity along the venom duct, including regions with a dense layer of secretory cells and a small lumen and others with a looser cell arrangement and a larger lumen, which could support such regional specialization. Gomori’s Trichrome stain shows muscle fibres in red, collagen in green and nuclei in blue/black (scale bar, 20 μm). (f) A simple hypothesis to explain the generation of separate stimulus-evoked venoms is proposed. An initial stimulus (predatory or defensive) is perceived by mechanical, visual and/or chemical (olfactory) sensors that transmit information to the cerebral ganglia surrounding the oesophagus (O) to activate two separate neuronal circuits. Predation-evoked stimuli activate neuronal circuit (blue) innervating the distal venom duct, causing the release of predatory venom peptides into the venom duct lumen. Similarly, threats including larger fish and cephalopods activate a separate defensive neuronal circuit (green) that innervates the proximal venom duct, causing the release of defensive toxins into the lumen. These lumen contents are then moved to the proboscis by a synchronized contraction of the muscular venom bulb to generate the injected ‘predation-evoked’ and ‘defence-evoked’ venoms. This key role of the venom bulb allows the rapid switch between the predation- and defence-evoked venoms observed. This mechanism of stimulus-dependent release of toxins from different sections of the venom duct explains how distinct predation- and defence-evoked venoms are generated.
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Related In: Results  -  Collection

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f3: Distribution of toxins in C. geographus venom duct and proposed mechanism for venom release.(a) Twelve venom gland sections were spotted on a MALDI plate together with predation- and defence-evoked venom (O, oesophagus; P, proboscis; RS, radular sac; SG, salivary gland). (b) The resulting averaged spectrum is highly complex in the range 1,000–4,000 kDa corresponding to the size of most conotoxins (10–30 amino acids). (c) Gel view representation of MALDI results reveals distinct regionalization of many venom components along the duct. For example, the predatory toxin at 3,175 kDa and defensive toxin at 1,417 kDa show clear non-overlapping distribution along the duct. (d) Quantification of five major predatory (including conopressin-G at 1,035 kDa) and defensive (including α-GII at 1,417 kDa, μ-GIIIA at 2,610 kDa and ω-GVIIA at 3,316 kDa) toxins confirms this region-specific toxin production. (e) Histology (formaldehyde-fixed animal embedded in paraffin) reveals structural heterogeneity along the venom duct, including regions with a dense layer of secretory cells and a small lumen and others with a looser cell arrangement and a larger lumen, which could support such regional specialization. Gomori’s Trichrome stain shows muscle fibres in red, collagen in green and nuclei in blue/black (scale bar, 20 μm). (f) A simple hypothesis to explain the generation of separate stimulus-evoked venoms is proposed. An initial stimulus (predatory or defensive) is perceived by mechanical, visual and/or chemical (olfactory) sensors that transmit information to the cerebral ganglia surrounding the oesophagus (O) to activate two separate neuronal circuits. Predation-evoked stimuli activate neuronal circuit (blue) innervating the distal venom duct, causing the release of predatory venom peptides into the venom duct lumen. Similarly, threats including larger fish and cephalopods activate a separate defensive neuronal circuit (green) that innervates the proximal venom duct, causing the release of defensive toxins into the lumen. These lumen contents are then moved to the proboscis by a synchronized contraction of the muscular venom bulb to generate the injected ‘predation-evoked’ and ‘defence-evoked’ venoms. This key role of the venom bulb allows the rapid switch between the predation- and defence-evoked venoms observed. This mechanism of stimulus-dependent release of toxins from different sections of the venom duct explains how distinct predation- and defence-evoked venoms are generated.
Mentions: The long, convoluted venom duct is the dominant toxin secretory organ in cone snails, but it is unclear if other embryologically related organs might also participate in venom production12. Analyses of the transcriptomes and proteomes of the interconnected venom gland, salivary gland and radular sac of C. geographus unequivocally demonstrated that both predation- and defence-evoked venoms arise from the venom duct and not these other associated tissues (Supplementary Figs 12 and 13), with 127 conotoxin sequences recovered from the venom duct, including 43 confirmed by tandem mass spectrometry (MS/MS) (Supplementary Table 1). In contrast, no conotoxin sequences were found in the salivary gland, and only three rare conotoxin transcripts were identified in the radula sac transcriptome, although these were not detected in the injected venoms. To understand how a single gland can rapidly and reversibly produce two distinct venoms, we analysed the venom peptide composition along the venom duct of C. geographus (Fig. 3a–c). Unexpectedly, the paralytic toxins found in the defence-evoked venom were abundant in the proximal duct (sections 7–12), whereas the major toxins found in the predation-evoked venom dominated the distal sections (sections 1–6 close to the pharynx) (Fig. 3d, Supplementary Fig. 14). In addition, structural differences within the venom duct support the distinct partition of the gland producing toxins (Fig. 3e). These results suggest that stimulus-dependent spatiotemporal release of toxins from different segments of the venom duct can generate functionally and biochemically distinct predation- and defence-evoked venoms (Fig. 3f).

Bottom Line: Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans.Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms.We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072 Queensland, Australia [2] Institut des Biomolécules Max Mousseron, UMR 5247, Université Montpellier 2-CNRS, Place Eugène Bataillon, Montpellier Cedex 5 34095, France.

ABSTRACT
Venomous animals are thought to inject the same combination of toxins for both predation and defence, presumably exploiting conserved target pharmacology across prey and predators. Remarkably, cone snails can rapidly switch between distinct venoms in response to predatory or defensive stimuli. Here, we show that the defence-evoked venom of Conus geographus contains high levels of paralytic toxins that potently block neuromuscular receptors, consistent with its lethal effects on humans. In contrast, C. geographus predation-evoked venom contains prey-specific toxins mostly inactive at human targets. Predation- and defence-evoked venoms originate from the distal and proximal regions of the venom duct, respectively, explaining how different stimuli can generate two distinct venoms. A specialized defensive envenomation strategy is widely evolved across worm, mollusk and fish-hunting cone snails. We propose that defensive toxins, originally evolved in ancestral worm-hunting cone snails to protect against cephalopod and fish predation, have been repurposed in predatory venoms to facilitate diversification to fish and mollusk diets.

Show MeSH
Related in: MedlinePlus