Origin and Evolution of Venom in Squamate Reptiles

Reptile venoms have become a central focus of biological research for two fundamentally different reasons: for public health, venomous snakes are of considerable importance, and for evolutionary research, where venoms provide exemplary systems for studying the links between genotype, biochemical phenotype, and environment. The advent of -omics technologies has enabled major advances in our understanding of the evolution of reptile venoms and their regulatory mechanisms. Here, we reanalyze evidence on the early evolution of venom in squamates and find support for multiple independent origins, rather than a single origin. We review the current state of knowledge on the evolution of toxin genes, the selective drivers of venom evolution, and the regulatory mechanisms controlling the synthesis of venom from the information contained in the genome. We stress that, while -omics technologies have revolutionized our knowledge of venom evolution, understanding the natural history of reptile venoms remains crucial to resolving key points of uncertainty in reptile venom evolution.