Mahdokht Jouiaei, Kartik Sunagar, Aya Federman Gross, Holger Scheib, Paul F. Alewood, Yehu Moran, Bryan G. Fry Take a look at our paper in MBE where we show that Cndarian toxins remain conserved despite their long evolutionary history and that Potassium ion-channel targeting toxins have evolved from the Sodium ion-channel targeting toxins in Actinioidea ( sea anemone) << Get the paper here >> Despite Cnidaria (sea anemones, corals, jellyfish, and hydroids) being the oldest venomous animal lineage, structure–function relationships, phyletic distributions, and the molecular evolutionary regimes of toxins encoded by these intriguing animals are poorly understood. Hence, we have comprehensively elucidated the phylogenetic and molecular evolutionary histories of pharmacologically characterized cnidarian toxin families, including peptide neurotoxins (voltage-gated Na+ and K+ channel-targeting toxins: NaTxs and KTxs, respectively), pore-forming toxins (actinoporins, aerolysin-related toxins, and jellyfish toxins), and the newly discovered small cysteine-rich peptides (SCRiPs). We show that despite long evolutionary histories, most cnidarian toxins remain conserved under the strong influence of negative selection—a finding that is in striking contrast to the rapid evolution of toxin families in evolutionarily younger lineages, such as cone snails and advanced snakes. In contrast to the previous suggestions that implicated SCRiPs in the biomineralization process in corals, we demonstrate that they are potent neurotoxins that are likely involved in the envenoming function, and thus represent the first family of neurotoxins from corals. We also demonstrate the common evolutionary origin of type III KTxs and NaTxs in sea anemones. We show that type III KTxs have evolved from NaTxs under the regime of positive selection, and likely represent a unique evolutionary innovation of the Actinioidea lineage. We report a correlation between the accumulation of episodically adaptive sites and the emergence of novel pharmacological activities in this rapidly evolving neurotoxic clade.
Casewell NRC*, Jackson TMW*, Laustsen A*, and Sunagar K* << Get the paper here >> Snake venoms are mixtures of toxins that vary extensively between and within snake species. This variability has serious consequences for the management of the world’s 1.8 million annual snakebite victims. Advances in ‘omic’ technologies have empowered toxinologists to comprehensively characterize snake venom compositions, unravel the molecular mechanisms that underpin venom variation, and elucidate the ensuing functional consequences. In this review, we describe how such mechanistic processes have resulted in suites of toxin isoforms that cause diverse pathologies in human snakebite victims and we detail how variation in venom composition can result in treatment failure. Finally, we outline current therapeutic approaches designed to circumvent venom variation and deliver next-generation treatments for the world’s most lethal neglected tropical disease.
Casewell NR, Petras D, Card DC, Suranse V, Mychajliw AM, Richards D, Koludarov I, Albulescu L-O, Slagboom J, Hempel B-F, Ngum NM, Kennerley RJ, Brocca JL, Whiteley G, Harrison RA, Bolton FMS, Debono J, Vonk FJ, Alföldi J, Johnson J, Karlsson EK, Lindblad-Toh K, Mellor IR, Süssmuth RD, Fry BG, Kuruppu S, Hodgson WC, Kool J, Castoe TA, Barnes I, Sunagar K, Undheim EAB and Turvey ST. << Download the paper here >> Multiple representatives of eulipotyphlan mammals (shrews, hedgehogs, moles, and solenodons) are venomous, but little is known about the evolutionary history and composition of their oral venom systems. Herein we characterized venom from the endangered Hispaniolan solenodon ( Solenodon paradoxus ) and find that it consists of hypotensive proteins likely used to facilitate vertebrate prey capture. We demonstrate that venom has evolved independently on at least 4 occasions in eulipotyphlans, and that molecular components of these venoms have also evolved convergently, with kallikrein-1 proteins coopted as toxins in both solenodons and shrews following their divergence over 70 million years ago. Our findings present an elegant example of convergent molecular evolution and highlight that mammalian venom systems may be subjected to evolutionary constraints.