Where did spiders get their venom?

The vast variety of toxins found in the venom of modern-day spiders evolved from a single small protein around 375 million years ago.

An orb-weaver spider from India. Image credit: Dr Kartik Sunagar (CC BY 4.0)

The majority of spiders rely on their venom to defend themselves, to hunt, or both. Armed with this formidable weapon, they have managed to conquer every continent besides Antarctica since they first emerged about 495 million years ago.

A closer look at spider venoms hints at an intriguing evolutionary history which has been rarely examined so far. The venom of other animals, such as snakes or scorpions, is usually formed of a wide range of unrelated toxins; in contrast, spiders rely on a single class of proteins, known as disulfide-rich peptides, to create their deadly venom cocktail. This family of molecules is impressively diverse, with each peptide having a distinct structure and mode of action. Its origins, however, have remained elusive.

To fill this knowledge gap, Shaikh and Sunagar scanned the sequences of all disulfide-rich peptides generated to date, bringing together a dataset that includes 60% of all modern-day spiders. The analyses allowed the identification of 78 new superfamilies of spider toxins. They also revealed that all existing peptides originate from a single molecule, which Shaikh and Sunagar named after the powerful Hindu goddess Adi Shakti. This ancestral toxin was present 375 million years ago in the last common ancestor of modern-day spiders.

The work also highlighted that disulfide-rich peptides evolved under different pressures in various groups of spiders; this may be because some species primarily use their venom for hunting, and others for defence. While the ‘hunters’ may need to constantly acquire toxins with new roles and structures to keep their edge over their prey, those that rely on venom to protect themselves may instead benefit from relying on tried-and-tested toxins useful against a range of infrequent predators. Finally, the analyses revealed that the disulphide-rich peptides of Mygalomorphae tarantulas, which form one of the three major groups of spiders, are much more diverse than the related toxins in other spiders. The underlying reason for this difference is still unclear.

Several life-saving drugs currently on the market are based on toxins first identified in the venoms of snakes, cone sails or lizards. Similar discoveries could be unlocked by better understanding the range of deadly molecules used by spiders, and how these came to be.