ABSTRACT

Venoms are complex integrated phenotypes used for predatory and defensive purposes by a wide range of organisms. Venoms represent fascinating systems to study fundamental evolutionary processes that transformed ordinary genes into deadly toxins. Research on venoms (“venomics”) has been continuously enhanced by advances in technology, and the increased use of sensitive proteomics techniques over the last decade has revolutionized venomics research. In this chapter, we discuss recent significant developments in the field of venomics that have contributed to a paradigm shift from single-species proteome analysis to the increasing trend towards comparative quantitative profiling of venom proteomes across whole genera or evolutionary clades. The emergence of top-down proteomic applications has allowed compositional resolution to be achieved at the level of the protein species present in the venom. On the other hand, a new hybrid configuration of elemental and molecular mass spectrometry has demonstrated the unique analytical ability to achieve absolute quantification of the venom proteome. Quantitative proteoform-resolved venom proteomes are needed to understand the spatio-temporal variability landscape underlying the adaptations that drive intraspecific venom evolution. Understanding the bio-logic of venoms is also of applied medical importance to treat human envenomings that occur in fortuitous encounters between humans and venomous organisms, such as snakes, scorpions or spiders. The challenges that remain to be solved in order to achieve a compact and automated platform with which routinely to carry out in a single run a comprehensive quantitative analysis of all toxins present in a venom, with the focus on snakes, are also discussed.