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Integrating Perspectives on Animal Venom Diversity: An Introduction to the Symposium.

Venom is a hallmark example of animal evolution: the capacity to make and use toxins has arisen via natural selection multiple times in animals as diverse as corals, snails, spiders, snakes, and mammals (Casewell et al. 2013). This diversity within the animal tree of life is mirrored by diversity at the molecular and genetic level, as the proteins that make up venoms and the genes that specify these proteins evolve rapidly to fill diverse functional roles (Sunagar et al. 2016). Because of their remarkable molecular diversity, venoms are key, albeit challenging, resource for pharmacological discovery that contribute to the development of drugs that act as anti-tumor agents, heart stimulants, and therapies for neurological diseases (Harvey 2014). Venom biology is a multidimensional field, spanning the molecules and genes of the phenotype to the ecological consequences of its use (Calvete 2013). Those dimensions are integrated in the organisms that make and use the venom. Although there have been previous symposia and working groups devoted to venom, these have focused on either a single organismal lineage (e.g., King 2004; Kem and Turk 2009) or limited methodological approaches (e.g., Escoubas 2006; Calvete 2012). This symposium aimed to span the lineages and organizational levels at which venom is being studied and to develop links between these levels and across these lineages. All venoms are similar in being complex cocktails of proteins and other bioactive compounds that are injected by the manufacturing animal into another animal (Casewell et al. 2013). Even when venom is not homologous in a broad evolutionary sense, the genes that are recruited into venom may belong to the same gene families. Similarities in molecular targets and the need for functional redundancy for neofunctionalizing genes may limit the pool of possible gene families from which venom genes can be recruited (Fry et al. 2009). However, as Rodrı́guez de la Vega points out in his symposium contribution, because toxins may be recruited convergently from within the same large gene family, it is especially important to consider genes that encode non-toxin proteins or that are nonfunctional so as not to misinterpret the level of shared evolutionary history (Rodrı́guez de la Vega and Giraud 2016). This caution argues against exclusive or primary reliance on databases of genes and proteins linked to venom (e.g., ConoServer: Kaas et al. 2011; ToxProt: Jungo et al. 2012) as the source of genes and proteins for comparison and underscores the importance of genomic (rather than transcriptomic) approaches to understanding the molecular origin of venom (Reyes-Velasco et al. 2015). Although these databases are an important resource for detecting and interpreting the genes that contribute to venoms, for contextualizing the genes that encode venoms, coding genes without venom function and pseudogenes are likely as important as genes with known function in venom. The biochemical diversity of venoms poses a compelling system in which to understand the genetic and molecular origin of diversity and the ecological and evolutionary impact of this diversity (Sunagar et al. 2016). This is best understood for snakes and other lineages which have been more completely studied because they have a direct impact on human health. Nonetheless, for even these well Integrative and Comparative Biology