The strong correlation between protein levels in the two parental species and in the hybrids indicates that venom levels are genetically controlled (Fig. 5).
Coagulopathy was defined as platelet count less than 150,000/mm, fibrinogen less than 150 mg/dL, or use of antivenom to treat a coagulation abnormality between the end of maintenance dosing and study day 5. Secondary efficacy endpoints included platelet counts, fibrinogen levels, and venom levels.
At the full-venom level, transcriptional effort among toxin classes was found to be dramatically different between C. horridus and C. adamanteus, and this same pattern repeated itself at a finer scale among paralogs within toxin classes.
This also suggests that changes in venom component levels, rather than protein sequence-level changes, may be the most rapid and effective way for snakes to exploit new prey species.
Direct analysis of venom nucleoside levels would be required to determine what level of mRNA expression corresponds to a departure from metabolic function to envenomation.
Although our measure of protein abundance was relatively crude, we were nonetheless able to detect a correlation (Protobothrops flavoviridis r = 0.77, p < 2.2e-16; okinavensisnavensis r = 0.70, p < 1.1e-12) between mRNA and venom protein levels.
We propose that regulation of venom constituent levels may be a major short-term mechanism by which snakes adapt to new prey types, and may be a driver of protein molecular evolution.
Additive effects, as opposed to dominance and epistatic effects, are particularly good targets for natural selection [ 112], though, more generally, genetic control of venom constituent levels makes them a potential target for natural selection.
Hybrid venom protein levels are largely intermediate between those of the parental species, suggesting that each component may be largely additively regulated, though there is also evidence that hybrids show higher levels of proteins, relative to the two parental species, perhaps a manifestation of "hybrid vigor".
