The structural and functional divergence of a neglected three-finger toxin subfamily in lethal elapids

Bungarus multicinctus is a widely distributed and medically important elapid snake that produces lethal neurotoxic venom. To study and enhance existing antivenom, we explore the complete repertoire of its toxin genes based on de novo chromosome-level assembly and multi-tissue transcriptome data. Comparative genomic analyses suggest that the three-finger toxin family (3FTX) may evolve through the neofunctionaliza-tion of flanking LY6E. A long-neglected 3FTX subfamily (i.e., MKA-3FTX) is also investigated. Only one MKA-3FTX gene, which evolves a different protein conformation, is under positive selection and actively transcribed in the venom gland, functioning as a major toxin effector together with MKT-3FTX subfamily homologs. Furthermore, this lethal snake may acquire self-resistance to its b-bungarotoxin via amino acid replacements on fast-evolving KCNA2. This study provides valuable resources for further evolutionary and structure-function studies of snake toxins, which are fundamental for the development of effective antive-noms and drug candidates.

Automated summary

This study explores the toxin genes of the medically important Bungarus multicinctus snake, revealing the role of the three-finger toxin family and the previously neglected MKA-3FTX subfamily in producing lethal venom. It also suggests that the snake may have developed self-resistance to its own toxin through adaptive amino acid replacements on the KCNA2 gene.