Differential Hematotoxic Activity of Southeast Asian Pit Viper Venoms: The Cross-Neutralizing Effect of Available Antivenoms

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  Image Credit: Creative Commons (some rights reserved) CC BY-NC Photo 111998430, (c) Nicholas Hess Differential Hematotoxic Activity of Southeast Asian Pit Viper Venoms: The Cross-Neutralizing Effect of Available Antivenoms Abstract Background/Objectives : Pit vipers (subfamily Crotalinae) are responsible for a large proportion of snakebite envenoming cases in Southeast Asia. Envenomation by these snakes commonly causes hematotoxic effects, including platelet dysfunction and coagulation disturbances. Although antivenom remains the mainstay of treatment, species-specific antivenoms are not available for several regional pit viper species. This study evaluated the hematotoxic activities of selected Southeast Asian pit viper venoms and the cross-neutralizing capacity of commercially available antivenoms.  Methods : Venoms from five medically important pit viper species— Calloselasma rhodostoma ,  Trimeresurus albolabris ,  T. hageni ,  T. purpureomaculatus , ...

Ancient origin and dynamic evolution of bivalent spider toxins

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Ancient origin and dynamic evolution of bivalent spider toxins

Abstract

Bivalent peptide toxins comprising two cysteine-rich domains have evolved from single-domain precursors on multiple occasions in animal venoms, resulting in enhanced molecular target selectivity and avidity. Although bivalent toxins are emerging as prevalent in animal venoms, the genomic and evolutionary processes driving the transitions between single- and multi-domain architectures remain poorly understood. Here, we investigated the evolution of bivalent inhibitor cystine knot (ICK) toxins in spider venom. We first generated a genome assembly of the tree-dwelling funnel-web spider Hadronyche cerberea, revealing a massive expansion of ICK toxin-encoding genes, including the bivalent π-hexatoxin-Hc1a. All ICK toxin genes share a conserved three-exon-structure, flanked by transposable elements (TEs) that may have facilitated gene expansion. This gene structure is shared by the Hc1a subfamily, where the entire mature bivalent toxin is encoded by the third exon. Leveraging de novo transcriptome assemblies from 86 spider species along with venom proteomic data, we show that bivalency in the Hc1a subfamily is of ancient origin and evolved via intra-exonic duplication not involving introns. This was followed by domain expansion and recurrent domain losses mediated by point mutations, deletions, and unequal crossing-over facilitated by high interdomain sequence similarity. In contrast, the bivalent toxin DkTx from Cyriopagopus schmidti is confined to a small group of tarantulas, where it appears to have evolved once, with subsequent domain losses potentially linked to TE activity. Our findings reveal that singular events of domain duplication can give rise to complex, asymmetrical evolutionary trajectories shaped by gene instability and selective retention of functional domains.

Araya, R. A., Maurstad, M. F., Wilson, D., Rash, L. D., Mobli, M., Jakobsen, K. S., & Undheim, E. A. Ancient origin and dynamic evolution of bivalent spider toxins. Molecular Biology and Evolution. https://doi.org/10.1093/molbev/msag076