Venom systems are among nature's most sophisticated biological innovations, yet their evolution and functional integration remain incompletely understood. We conducted a large-scale comparative analysis of venom-related genes across animals using phylogenetic and genomic approaches.
We compiled a dataset of venom-associated protein families from public databases, spanning diverse taxa to capture broad evolutionary patterns. To identify coevolving proteins, we applied phylogenetic profiling, representing each gene as a binary vector encoding its presence or absence across species. By comparing these profiles, we detected protein families with similar evolutionary trajectories. Using the Metazoa dataset from the OMA database, which uses hierarchical orthologous groups (HOGs), we employed the HogProf algorithm to identify HOGs with high similarity to venom-related profiles. This enabled systematic detection of candidate genes potentially involved in venom function or self-resistance.
Preliminary results show that proteins within the same venom cocktail often share highly similar phylogenetic profiles, supporting coordinated evolution. We also observed a correlation between expression patterns and phylogenetic similarity, suggesting functional links. Additionally, we identified protein families with venom-like evolutionary signatures not currently associated with venom, highlighting candidates for resistance mechanisms.
A central aim is to understand how venomous species avoid self-intoxication through biochemical adaptations. Investigating these mechanisms may clarify the evolutionary interplay between toxin production and resistance, and provide broader insight into the evolution of toxin resistance across species.

Co-authors: Giulia Zancolli, Christophe Dessimoz, Natasha Glover