Dataset Information

The lethal toxin from Australian funnel-web spiders is encoded by an intronless gene.

ABSTRACT: Australian funnel-web spiders are generally considered the most dangerous spiders in the world, with envenomations from the Sydney funnel-web spider Atrax robustus resulting in at least 14 human fatalities prior to the introduction of an effective anti-venom in 1980. The clinical envenomation syndrome resulting from bites by Australian funnel-web spiders is due to a single 42-residue peptide known as ?-hexatoxin. This peptide delays the inactivation of voltage-gated sodium channels, which results in spontaneous repetitive firing and prolongation of action potentials, thereby causing massive neurotransmitter release from both somatic and autonomic nerve endings. Here we show that ?-hexatoxin from the Australian funnel-web spider Hadronyche versuta is produced from an intronless gene that encodes a prepropeptide that is post-translationally processed to yield the mature toxin. A limited sampling of genes encoding unrelated venom peptides from this spider indicated that they are all intronless. Thus, in distinct contrast to cone snails and scorpions, whose toxin genes contain introns, spiders may have developed a quite different genetic strategy for evolving their venom peptidome.

SUBMITTER: Pineda SS

PROVIDER: S-EPMC3425536 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The lethal toxin from Australian funnel-web spiders is encoded by an intronless gene.

Pineda Sandy Steffany SS Wilson David D Mattick John S JS King Glenn F GF

PloS one 20120822 8

Australian funnel-web spiders are generally considered the most dangerous spiders in the world, with envenomations from the Sydney funnel-web spider Atrax robustus resulting in at least 14 human fatalities prior to the introduction of an effective anti-venom in 1980. The clinical envenomation syndrome resulting from bites by Australian funnel-web spiders is due to a single 42-residue peptide known as δ-hexatoxin. This peptide delays the inactivation of voltage-gated sodium channels, which result ...[more]

PMID: 22928020

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Project description:BACKGROUND: Spiders have evolved pharmacologically complex venoms that serve to rapidly subdue prey and deter predators. The major toxic factors in most spider venoms are small, disulfide-rich peptides. While there is abundant evidence that snake venoms evolved by recruitment of genes encoding normal body proteins followed by extensive gene duplication accompanied by explosive structural and functional diversification, the evolutionary trajectory of spider-venom peptides is less clear. RESULTS: Here we present evidence of a spider-toxin superfamily encoding a high degree of sequence and functional diversity that has evolved via accelerated duplication and diversification of a single ancestral gene. The peptides within this toxin superfamily are translated as prepropeptides that are posttranslationally processed to yield the mature toxin. The N-terminal signal sequence, as well as the protease recognition site at the junction of the propeptide and mature toxin are conserved, whereas the remainder of the propeptide and mature toxin sequences are variable. All toxin transcripts within this superfamily exhibit a striking cysteine codon bias. We show that different pharmacological classes of toxins within this peptide superfamily evolved under different evolutionary selection pressures. CONCLUSIONS: Overall, this study reinforces the hypothesis that spiders use a combinatorial peptide library strategy to evolve a complex cocktail of peptide toxins that target neuronal receptors and ion channels in prey and predators. We show that the ?-hexatoxins that target insect voltage-gated calcium channels evolved under the influence of positive Darwinian selection in an episodic fashion, whereas the ?-hexatoxins that target insect calcium-activated potassium channels appear to be under negative selection. A majority of the diversifying sites in the ?-hexatoxins are concentrated on the molecular surface of the toxins, thereby facilitating neofunctionalisation leading to new toxin pharmacology.

Project description:Mygalomorph venom properties and active components, which have importance in medicine, agronomy, venomics, ecology and evolution, have been widely studied, but only a small fraction have been characterised. Several studies have shown inter-individual variation in the composition of venom peptides based on ontogeny, sexual dimorphism, season and diet. However, intra-individual variation in venom composition, which could play a key role in the evolution, diversification and function of toxins, is poorly understood. In this study, we demonstrate significant intra- and inter-individual variation in venom composition in the Australian funnel-web spider Hadronyche valida, highlighting that individuals show different venom profiles over time. Fourteen (four juvenile and ten adult females) funnel-web spiders, maintained under the same environmental conditions and diet, were milked a total of four times, one month apart. We then used reversed-phase high performance liquid chromatography/electrospray ionisation mass spectrometry to generate venom fingerprints containing the retention time and molecular weights of the different toxin components in the venom. Across all individuals, we documented a combined total of 83 individual venom components. Only 20% of these components were shared between individuals. Individuals showed variation in the composition of venom peptides, with some components consistently present over time, while others were only present at specific times. When individuals were grouped using the Jaccard clustering index and Kernel Principal Component Analysis, spiders formed two distinct clusters, most likely due to their origin or time of collection. This study contributes to the understanding of variation in venom composition at different levels (intra-individual, and intra- and inter-specific) and considers some of the mechanisms of selection that may contribute to venom diversification within arachnids. In addition, inter-specific variation in venom composition can be highly useful as a chemotaxonomic marker to identify funnel-web species.

Project description:Australian funnel-web spiders are iconic species, characterized as being the most venomous spiders in the world. They are also valued for the therapeutics and natural bioinsecticides potentially hidden in their venom molecules. Although numerous biochemical and molecular structural approaches have tried to determine the factors driving venom complexity, these approaches have not considered behaviour, physiology and environmental conditions collectively, which can play a role in the evolution, complexity, and function of venom components in funnel-webs. This study used a novel interdisciplinary approach to understand the relationships between different behaviours (assessed in different ecological contexts) and morphophysiological variables (body condition, heart rate) that may affect venom composition in four species of Australian funnel-web spiders. We tested defensiveness, huddling behaviour, frequency of climbing, and activity for all species in three ecological contexts: i) predation using both indirect (puff of air) and direct (prodding) stimuli; ii) conspecific tolerance; and iii) exploration of a new territory. We also assessed morphophysiological variables and venom composition of all species. For Hadronyche valida, the expression of some venom components was associated with heart rate and defensiveness during the predation context. However, we did not find any associations between behavioural traits and morphophysiological variables in the other species, suggesting that particular associations may be species-specific. When we assessed differences between species, we found that the species separated out based on the venom profiles, while activity and heart rate are likely more affected by individual responses and microhabitat conditions. This study demonstrates how behavioural and morphophysiological traits are correlated with venom composition and contributes to a broader understanding of the function and evolution of venoms in funnel-web spiders.

Dataset Information

The lethal toxin from Australian funnel-web spiders is encoded by an intronless gene.

Publications

The lethal toxin from Australian funnel-web spiders is encoded by an intronless gene.

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