Dominant toxin hypothesis: unravelling the venom phenotype across micro and macroevolution

Abstract

Venom is a complex trait with substantial inter- and intraspecific variability resulting from strong selective pressures acting on the expression of many toxic proteins. However, understanding the processes underlying the toxin expression dynamics that determine the venom phenotype remains unresolved. Here, we use comparative genomics and transcriptomics to reveal that toxin expression in sea anemones evolves rapidly with little constraint and that a single toxin family dictates the venom phenotype in each species. This dominant toxin family is characterized by massive gene duplication events. In-depth analysis of the sea anemone, Nematostella vectensis, revealed significant variation in the number of copies of the dominant toxin (Nv1) across populations, corresponding to significant differences in Nv1 expression at both the transcript and protein levels. These differences in Nv1 copies are driven by independent expansion events, resulting in distinct haplotypes that have a restricted geographical distribution. Strikingly, one population has undergone a severe contraction event, causing a near-complete loss of Nv1 production. Our findings across micro- and macroevolutionary scales in sea anemones complement observations of single dominant toxin family present in other venomous organisms and establishes the dominant toxin hypothesis whereby venomous animals have convergently evolved a similar strategy in shaping the venom phenotype.