Snake venomics: from the inventory of toxins to biology.

A deep understanding of the composition of venoms and of the principles governing the evolution of venomous systems is of applied importance for exploring the enormous potential of venoms as sources of chemical and pharmacological novelty but also to fight the dire consequences of snakebite envenomings. This goal is now within the reach of "omic" technologies. A central thesis developed in this essay is the view that making sense of the huge inventory of data gathered through "omic" approaches requires the integration of this information across the biological system. Key to this is the identification of evolutionary and ecological trends; without the evolutionary link, systems venomics is relegated to a set of miscellaneous facts. The interplay between chance and adaptation plays a central role in the evolution of biological systems (Monod, 1970). However, the evolution of venomous species and their venoms do not always follow the same course, and the identification of structural and functional convergences and divergences among venoms is often unpredictable by a phylogenetic hypothesis. Toxins sharing a structural fold present in venoms from phylogenetically distant snakes often share antigenic determinants. The deficit of antivenom supply in certain regions of the world can be mitigated in part through the optimized use of existing antivenoms, and through the design of novel broad-range polyspecific antivenoms. Proteomics-guided identification of evolutionary and immunoreactivity trends among homologous and heterologous venoms may aid in the replacement of the traditional geographic- and phylogenetic-driven hypotheses for antivenom production strategies by a more rationale approach based on a hypothesis-driven systems venomics approach. Selected applications of venomics and antivenomics for exploring the chemical space and immunological profile of venoms will illustrate the author's views on the impact these proteomics tools may have in the field of toxinology.