Abstract
BackgroundSpiders 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.ResultsHere 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.ConclusionsOverall, 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 ω-hexatoxins that target insect voltage-gated calcium channels evolved under the influence of positive Darwinian selection in an episodic fashion, whereas the κ-hexatoxins that target insect calcium-activated potassium channels appear to be under negative selection. A majority of the diversifying sites in the ω-hexatoxins are concentrated on the molecular surface of the toxins, thereby facilitating neofunctionalisation leading to new toxin pharmacology.
Highlights
Spiders have evolved pharmacologically complex venoms that serve to rapidly subdue prey and deter predators
The ω-hexatoxins are expressed as prepropeptide precursors Rapid amplification of cDNA ends (RACE) analysis was used to amplify transcripts encoding orthologs of ω-Omega hexatoxins (HXTX)-Hv1a from four species of Australian funnel-web spider: Atrax robustus, H. infensa, H. venenata, and H. versuta (Figure 2)
Multiple ω-HXTX-Hv1a orthologs were identified in each species (i.e., 24 paralogs encoding seven distinct mature toxins were identified in H. infensa, 18 paralogs encoding six mature toxins were identified in the Sydney funnel-web spider A. robustus, and eight paralogs encoding two mature toxins identified in the Tasmanian funnel-web spider H. venenata) (Figure 3A)
Summary
Spiders have evolved pharmacologically complex venoms that serve to rapidly subdue prey and deter predators. There is abundant evidence that snake venoms evolved by recruitment of genes encoding normal body proteins followed by extensive duplication, neofunctionalization, and in some instances relegation to the status of pseudogene [1,3,4,5] In many cases, these genes have been explosively replicated to produce large multigene families. The evolutionary trajectory is less clear for the venoms of spiders, scorpions, and molluscs, which are dominated by disulfide-rich peptides of mass 2–9 kDa [7,8,9,10,11,12] These peptides typically possess high affinity and often-exquisite specificity for particular classes of ion channels and other nervous system targets [13,14,15]. These neurotoxic functions are perhaps not surprising given that the primary role of these venoms is to paralyse or kill envenomated prey [11,16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
