Comparative venomics suggests an evolutionary adaption of spider venom from predation to defense

Most spiders deploy paralytic venom for prey capture, but adults of the Nurse´s thorn finger (Cheiracanthium punctorium) instead produce a predominantly defensive venom to safeguard their offspring. Here, we characterize 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 shows that CSTXs arise following the mygalomorph–araneomorph split ~300 mya by means of ancestral gene duplication and functional specialization. A gene fusion event then appeared to have merged CSTXs from two distinct clades to form the double-domain toxin. PLA2 proteins are 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 nature’s tendency to use the same molecular solutions for similar ecological challenges across diverse animal lineages.