Production and packaging of a biological arsenal: Evolution of centipede venoms under morphological constraint

Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph centipedes produce less complex venom than those secreted by scolopendrid centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought. Significance Venom peptides have attracted considerable attention because of their value as pharmacological tools and their potential for development as novel pharmaceuticals and bioinsecticides. There is also a growing interest in venoms as model evolutionary systems, particularly for understanding antagonistic coevolutionary processes. We previously demonstrated that although centipede venoms are rich in novel proteins and peptides, there are considerable differences in venom complexity between high-order taxa. We show that this disparity appears to stem from morphological limitations of the venom gland, and that most centipede venoms likely evolve under constraints imposed by low-complexity toxin production facilities. Thus, the centipede venom apparatus should be a useful model system for gaining insight into th