Low extent of sex-based venom variation in Earth's most widespread viper, the common adder (Vipera berus)

Schulte, L.; Engelhardt, M.; Eichberg, J.; Cabrera-Orefice, A.; Wölfel, H.; Damm, M.; Avella, I.; Kreuels, B.; Hardes, K.; Eble, J. A.; Vilcinskas, A.; Lüddecke, T.

doi:10.1101/2025.03.27.645687

bioRxiv · 10.1101/2025.03.27.645687

Low extent of sex-based venom variation in Earth's most widespread viper, the common adder (Vipera berus)

Schulte, L.·Engelhardt, M.·Eichberg, J.·Cabrera-Orefice, A.·Wölfel, H.·Damm, M.·Avella, I.·Kreuels, B.·Hardes, K.·Eble, J. A.·Vilcinskas, A.·Lüddecke, T.

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Abstract

Snake venom is an ecologically critical functional trait, primarily applied for foraging and accordingly shaped by selective pressures. Recent insights underpinned the high variability of snake venoms down to the intraspecific level, with regional, ontogenetic, and seasonal variation being mostly investigated. In contrast, sex-based venom variation has received considerably less attention so far, and its influence on venom compositions in vipers is virtually unknown. The common adder (Vipera berus) is a promising model species to explore this subject because of a described sexual dimorphism and its wide distribution, which promises a noteworthy degree of adaptability and venom plasticity. Here, we tested for sex-based venom variation in Central European V. berus by comparing venom profiles and bioactivity. Proteomics, paired with SDS-PAGE and RP-HPLC, revealed highly similar venom profiles. Likewise, phospholipases A2 and proteases bioactivity profiling, and bioassays targeting the coagulation cascade and mammalian cell lines revealed similar activity spectra. Hence, our analysis does not show a noteworthy extent of sex-based intraspecific venom variation in V. berus. We further discuss our data in light of the species venom profile at larger geographic scales, its clinical relevance, and the need for more standardized approaches when investigating venom variability. Our work provides novel insights into the venom biology of Earths most widespread viper, and serves as a foundation upon which future works can build.

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Schulte, L., Engelhardt, M., Eichberg, J., Cabrera-Orefice, A., Wölfel, H., Damm, M., Avella, I., Kreuels, B., Hardes, K., Eble, J. A., Vilcinskas, A., Lüddecke, T.. 2025-03-29. Low extent of sex-based venom variation in Earth's most widespread viper, the common adder (Vipera berus). https://doi.org/10.1101/2025.03.27.645687

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