| Summary: | Snakes of the Philodryadini tribe are included in the Dipsadidae family, which is a diverse group of rear-fanged snakes widespread in different ecological conditions, including habitats and diet. However, little is known about the composition and effects of their venoms despite their relevance for understanding the evolution of these snakes or even their impact on the occasional cases of human envenoming. In this study, we integrated venom gland transcriptomics, venom proteomics and functional assays to characterize the venoms from eight species of the Philodryadini tribe, which includes the genus <i>Philodryas</i>, <i>Chlorosoma</i> and <i>Xenoxybelis</i>. The most abundant components identified in the venoms were snake venom metalloproteinases (SVMPs), cysteine-rich secretory proteins (CRISPs), C-type lectins (CTLs), snake endogenous matrix metalloproteinases type 9 (seMMP-9) and snake venom serinoproteinases (SVSPs). These protein families showed a variable expression profile in each genus. SVMPs were the most abundant components in <i>Philodryas</i>, while seMMP-9 and CRISPs were the most expressed in <i>Chlorosoma</i> and <i>Xenoxybelis</i>, respectively. Lineage-specific differences in venom composition were also observed among <i>Philodryas</i> species, whereas <i>P. olfersii</i> presented the highest amount of SVSPs and <i>P. agassizii</i> was the only species to express significant amounts of 3FTx. The variability observed in venom composition was confirmed by the venom functional assays. <i>Philodryas</i> species presented the highest SVMP activity, whereas <i>Chlorosoma</i> species showed higher levels of gelatin activity, which may correlate to the seMMP-9 enzymes. The variability observed in the composition of these venoms may be related to the tribe phylogeny and influenced by their diets. In the presented study, we expanded the set of venomics studies of the Philodryadini tribe, which paves new roads for further studies on the evolution and ecology of Dipsadidae snakes.
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