An insulin-like hormone in spiders and centipedes evolved independently, but with a similar pattern, to produce an insecticide toxin found in each of the organisms today.
Arthropods employ an extreme diversity of venoms. Many are neurotoxic insecticides and are used by organisms (that make you cringe) such as wasps, spiders, scorpions, centipedes, ticks, and some shellfish. Venom cocktails can be extremely potent and complex, sometimes made up of thousands of inorganic salts, biogenic amines, peptides, and proteins.
Despite the ubiquity of venoms and their widespread use as agricultural insecticides and medical drugs, little is known about the origins and evolution of venomous proteins. Many researchers hypothesize they are recruited from normal body proteins and isolated in the venom glands of an organism, where they gain new functions over time as their genes mutate (an important evolutionary process termed neofunctionalization).
To understand the origins of venom proteins, a collaborative research team from Australia and the U.S. studied a hormone family in the Funnel-web spider. This hormone family contains a group of venom proteins speculated to have arisen in spider venom some 375 million years ago. Interestingly, though the proteins in this group can all be found in venom, only one protein is known to be independently toxic: Ta1a.
The researchers homed in on Ta1a for their study of venom protein evolution, which was published in the journal Structure earlier this month. They found that the venom protein evolved from an insulin-like hormone that once helped the ancestors of the Funnel-web spider regulate carbohydrate metabolism.
The team came to this conclusion not by studying gene sequence identity (the normal method for detecting evolutionary relationships), but instead by identifying molecular structure. Since the gene sequence of Ta1a and the original hormone it evolved from diverged ~375 million years ago, the “signal” of their relatedness was masked by accumulated mutations.
But when the 3D structure of Ta1a was determined and used to search a database of known protein structures within the hormone family, the query produced a modern hormone that was almost identical in shape to Ta1a. Thus, since the shape and family of the original hormone and venom protein are shared, this hormone is the origin of the venom toxin.
To corroborate this finding, the researchers found that the centipede Scolopendra alternans recruited the same ancient hormone (spiders and centipedes share the ITP/CHH hormone family) and independently “invented” a venom protein in the same way as the Funnel-web spider. In fact, the structure of the centipede venom protein, Ssm6a, is almost identical to Ta1a as well as the original hormone from which they are derived.
Additionally, the researchers found that Ssm6a is one of the most persistent venom molecules ever described, lasting for over a week in human blood plasma. This shows it may provide a backbone structure for engineering stable drug or insecticide compounds in the future.
This study provides direct evidence supporting the neofunctionalization of body proteins into venoms. It highlights two convergent examples of the origin of a group of arthropod venom proteins and showed that, since venoms arise from proteins found natively in the body, two separate lineages (i.e. spiders and centipedes) sharing a particular protein can potentially evolve that protein into venom independently.