Data from: The molecular basis of venom resistance in a rattlesnake-squirrel predator-prey system

Understanding how interspecific interactions mould the molecular basis of
adaptations in coevolving species is a long-sought goal of evolutionary
biology. Venom in predators and venom resistance proteins in prey are
coevolving molecular phenotypes, and while venoms are highly complex
mixtures it is unclear if prey respond with equally complex resistance
traits. Here we use a novel molecular methodology based on protein
affinity columns to capture and identify candidate blood serum resistance
proteins (‘Venom Interactive Proteins’ – VIPs) in California Ground
Squirrels (Otospermophilus beecheyi) that interact with venom proteins
from their main predator, Northern Pacific Rattlesnakes (Crotalus o.
oreganus). This assay showed that serum-based resistance is both
population- and species-specific, with serum proteins from ground
squirrels showing higher binding affinities for venom proteins of local
snakes compared to allopatric individuals. Venom protein specificity
assays identified numerous and diverse candidate prey resistance VIPs but
also potential targets of venom in prey tissues. Many specific VIPs bind
to multiple snake venom proteins and, conversely, single venom proteins
bind multiple VIPs, demonstrating that a portion of the squirrel blood
serum “resistome” involves broad-based inhibition of non-self proteins and
suggests that resistance involves a toxin scavenging mechanism. Analyses
of rates of evolution of VIP protein homologs in related mammals show that
most of these proteins evolve under purifying selection possibly due to
molecular constraints that limit the evolutionary responses of prey to
rapidly evolving snake venom proteins. Our method represents a general
approach to identify specific proteins involved in coevolutionary
interactions between species at the molecular level.