Evolution of an ancient venom: Recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone

Mahdokht Jouiaei, Kartik Sunagar, Aya Federman Gross, Holger Scheib, Paul F. Alewood, Yehu Moran, Bryan G. Fry*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1598-1610
Number of pages13
JournalMolecular Biology and Evolution
Volume32
Issue number6
DOIs
StatePublished - 1 Jun 2015

Bibliographical note

Publisher Copyright:
© 2015 The Author 2015.

Keywords

  • Cnidaria
  • disulfide-rich toxins
  • phylogeny
  • positive selection
  • potassium channel toxins
  • sodium channel toxins

Fingerprint

Dive into the research topics of 'Evolution of an ancient venom: Recognition of a novel family of cnidarian toxins and the common evolutionary origin of sodium and potassium neurotoxins in sea anemone'. Together they form a unique fingerprint.

Cite this