Australian funnel-web spiders evolved human-lethal δ-hexatoxins for defense against vertebrate predators
Volker Herzig, Kartik Sunagar, David T. Wilson, Sandy S. Pineda, Mathilde R. Israel, Sébastien Dutertre, Brianna Sollod McFarland, Eivind A. B. Undheim, Wayne C. Hodgson, Paul F. Alewood, Richard J. Lewis, Frank Bosmans, Irina Vetter, Glenn F. King, Bryan G. Fry
Abstract
Significance The venom of Australian funnel-web spiders contains δ-hexatoxins (δ-HXTXs) that exert fatal neurotoxic effects in humans by inhibiting inactivation of voltage-gated sodium channels, but their precise ecological role remains unclear. Sequencing of venom-gland transcriptomes from 10 funnel-web species uncovered 22 δ-HXTXs. Evolutionary analysis revealed extreme conservation of these toxins, despite their ancient origin. We isolated the lethal δ-HXTX from venom of the Sydney funnel-web spider and showed that it induces pain in mice, suggesting a role in predator deterrence. Although humans are not the target of δ-HXTXs, these toxins likely evolved to deter vertebrate predators commonly encountered by these spiders, such as bandicoots, birds, and lizards. Thus, the lethal potency of δ-HXTXs against humans is an unfortunate evolutionary coincidence.