Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

Toxins

Kartik Sunagar¹  Kate Sanders²  Eivind A. B. Undheim³  Iwan Hendrikx³  Timothy N. W. Jackson³  Ivan Koludarov³  Angelo H. C. Chan³  Bryan G. Fry³  Syed A. Ali³  Nathan Dunstan⁴ 

[1] Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre, 4169-007, Porto, Portugal;School of Earth and Environmental Sciences, University of Adelaide, SA 5005, Australia;Venom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia QLD 4072, Australia;Venom Supplies Pty Ltd, Stonewell Rd, Tanunda SA 5352, Australia;

关键词: venom;    evolution;    phylogeny;    elapid;    Australia;    molecular evolution;    Darwinian selection;    toxin phylogenies;   

DOI  :  10.3390/toxins5122621

来源: DOAJ

【 摘 要 】

Despite the unparalleled diversity of venomous snakes in Australia, research has concentrated on a handful of medically significant species and even of these very few toxins have been fully sequenced. In this study, venom gland transcriptomes were sequenced from eleven species of small Australian elapid snakes, from eleven genera, spanning a broad phylogenetic range. The particularly large number of sequences obtained for three-finger toxin (3FTx) peptides allowed for robust reconstructions of their dynamic molecular evolutionary histories. We demonstrated that each species preferentially favoured different types of α-neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three forms of α-neurotoxin [Type I (also known as (aka): short-chain), Type II (aka: long-chain) and Type III] not only adopted differential rates of evolution, but have also conserved a diversity of residues, presumably to potentiate prey-specific toxicity. Despite these differences, the different α-neurotoxin types were shown to accumulate mutations in similar regions of the protein, largely in the loops and structurally unimportant regions, highlighting the significant role of focal mutagenesis. We theorize that this phenomenon not only affects toxin potency or specificity, but also generates necessary variation for preventing/delaying prey animals from acquiring venom-resistance. This study also recovered the first full-length sequences for multimeric phospholipase A2 (PLA2) ‘taipoxin/paradoxin’ subunits from non-Oxyuranus species, confirming the early recruitment of this extremely potent neurotoxin complex to the venom arsenal of Australian elapid snakes. We also recovered the first natriuretic peptides from an elapid that lack the derived C-terminal tail and resemble the plesiotypic form (ancestral character state) found in viper venoms. This provides supporting evidence for a single early recruitment of natriuretic peptides into snake venoms. Novel forms of kunitz and waprin peptides were recovered, including dual domain kunitz-kunitz precursors and the first kunitz-waprin hybrid precursors from elapid snakes. The novel sequences recovered in this study reveal that the huge diversity of unstudied venomous Australian snakes are of considerable interest not only for the investigation of venom and whole organism evolution but also represent an untapped bioresource in the search for novel compounds for use in drug design and development.

【 授权许可】

Unknown