Convergent evolutionary adaption of spider venom from predation to defense

Most spiders deploy paralytic venom for prey capture, but adults of the yellow-sac spider (Cheiracanthium punctorium) instead produce a predominantly defensive venom to safeguard their offspring. Here, we characterized the molecular repertoire of C. punctorium venom to shed light on its evolutionary history. Unlike venom in other spiders, C. punctorium venom mostly comprises neurotoxic double-domain neurotoxin 19 family (CSTX) peptides and enzymes, such as phospholipase A2 (PLA2). Comparative venomics in four spiders representing two infraorders showed that CSTXs arose following the mygalomorph- araneomorph split [~]300 mya by means of ancestral gene duplication and functional specialization. A gene fusion event then merged CSTXs from two distinct clades to form the double-domain toxin. PLA2 proteins were convergently recruited to C. punctorium to fulfil a defensive function and are strikingly similar to proalgesic PLA2 proteins in bee venom. These complex, multimodal molecular innovations in venom systems highlight natures tendency to use the same molecular solutions for similar ecological challenges across diverse animal lineages.