Animal venoms have fascinated humans for millennia, and for good reasons: injection of even miniscule amounts of certain venom components can result in rapid paralysis and death of animals. Not surprisingly, the evolution of venom, one of nature’s most complex biochemical concoctions, has underpinned the predatory success and diversification of numerous animal lineages. Animal venoms provide unparalleled models for understanding molecular adaptations associated with predator-prey interactions and the convergence of biochemical functions. Venoms are theorized to evolve under the significant influence of positive Darwinian selection in a chemical arms race scenario, where the evolution of venom resistance in prey and the invention of potent venom in the secreting animal exert reciprocal selection pressures. However, the dynamics of venom evolution and the mechanistic insights into the molecular changes that confer toxin resistance mostly remain elusive. We provide evidence of surprisingly constrained parallel molecular evolution across the animal kingdom, where the resistance to toxic cardiac glycosides produced by plants and bufonid toads is mediated by similar and predictable molecular changes to the sodium-potassium-pump (Na+/K+-ATPase) in several lineages of insects, amphibians, reptiles and mammals.
Understanding the genetic basis of the diversification of venom encoding genes in animals can provide fundamental biological insights into their species evolution, ecological specialization and genetic novelties, which may be of further importance for antivenom, pesticide development and drug-discovery research. However, venom research has mostly neglected ancient animal groups, such as spiders and centipedes in favour of focusing on venomous snakes and cone snails that originated relatively recently in the evolutionary timescale (~50 million years ago). By analysing over 3500 sequences from 85 toxin families in both ancient and evolutionarily young animals, we propose a new model of venom evolution that describes how venomous animals respond to evolutionary arms races and the significant shifts in ecology and environment. Our ‘two-speed’ model captures the fascinating ‘rise and fall’ in venom evolution.