Venom Resistance as a Model for Understanding the Molecular Basis of Complex Coevolutionary Adaptations

Synopsis Venom and venom resistance are molecular phenotypes widely considered to have diversified through coevolution between predators and prey. However, while evolutionary and functional studies on venom have been extensive, little is known about the molecular basis, variation, and complexity of venom resistance. We review known mechanisms of venom resistance and relate these mechanisms to their predicted impact on coevolutionary dynamics with venomous enemies. We then describe two conceptual approaches which can be used to examine venom/resistance systems. At the intraspecific level, tests of local adaptation in venom and resistance phenotypes can identify the functional mechanisms governing the outcomes of coevolution. At deeper evolutionary timescales, the combination of phylogenetically informed analyses of protein evolution coupled with studies of protein function promise to elucidate the mode and tempo of evolutionary change on potentially coevolving genes. We highlight case studies that use each approach to extend our knowledge of these systems as well as address larger questions about coevolutionary dynamics. We argue that resistance and venom are phenotypic traits which hold exceptional promise for investigating the mechanisms, dynamics, and outcomes of coevolution at the molecular level. Furthermore, extending the understanding of single gene-for-gene interactions to the whole resistance and venom phenotypes may provide a model system for examining the molecular and evolutionary dynamics of complex multi-gene interactions.