Lizards are major predators of arthropods, including chemically defended species such as spiders. We previously found two lizard species (Elgaria multicarinata, Sceloporus occidentalis) possess different degrees of resistance to black widow spider venom (BWSV). Because these lizards are not closely related, resistance might represent independent adaptations to local prey, or be a deeply rooted trait of lizards. To determine whether BWSV resistance is a derived or ancestral trait of lizards, we assessed BWSV resistance at organismal and tissue levels in three additional lizard species (Coleonyx variegatus, Takydromus sexlineatus, Iguana iguana) representing a broad phylogenetic, geographic, and ecological scope. We mapped results onto the lizard phylogeny and used a mammalian outgroup for comparison. To determine whether lizards might possess broad-spectrum resistance against many toxins, we also quantified resistance to Arizona bark scorpion venom (ABSV) in E. multicarinata and S. occidentalis. Sprint trials revealed that insectivorous species (C. variegatus, T. sexlineatus) were not significantly affected by BWSV, while the herbivorous species (I. iguana) exhibited severely reduced performance. Histological analysis showed minimal to moderate muscle damage in insectivorous species, but extensive damage in I. iguana. In comparison, sprint trials with E. multicarinata and S. occidentalis showed these lizards are highly susceptible to ABSV. As such, lizards are not broadly resistant to diverse toxins, but do possess a baseline level of resistance to BWSV compared to mammals, with resistance elevated in some lineages and lost in others. Thus, ecological interactions with widow spiders appear to have driven patterns of venom resistance across the lizard phylogeny.
Thill, V.L., Teglas, M.B., Moniz, H.A. et al. Ancient Enemies? Patterns of Resistance to Widow Spider Venom in Lizards. Evol Biol (2025). https://doi.org/10.1007/s11692-025-09650-1