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Venom down under: dynamic evolution of Australian elapid snake toxins.
Toxins (Basel). 2013 Dec 18; 5(12):2621-55.T

Abstract

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.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableVenom Evolution Lab, School of Biological Sciences, The University of Queensland, St. Lucia QLD 4072, Australia. bgfry@uq.edu.au.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24351719

Citation

Jackson, Timothy N W., et al. "Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins." Toxins, vol. 5, no. 12, 2013, pp. 2621-55.
Jackson TN, Sunagar K, Undheim EA, et al. Venom down under: dynamic evolution of Australian elapid snake toxins. Toxins (Basel). 2013;5(12):2621-55.
Jackson, T. N., Sunagar, K., Undheim, E. A., Koludarov, I., Chan, A. H., Sanders, K., Ali, S. A., Hendrikx, I., Dunstan, N., & Fry, B. G. (2013). Venom down under: dynamic evolution of Australian elapid snake toxins. Toxins, 5(12), 2621-55. https://doi.org/10.3390/toxins5122621
Jackson TN, et al. Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins. Toxins (Basel). 2013 Dec 18;5(12):2621-55. PubMed PMID: 24351719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Venom down under: dynamic evolution of Australian elapid snake toxins. AU - Jackson,Timothy N W, AU - Sunagar,Kartik, AU - Undheim,Eivind A B, AU - Koludarov,Ivan, AU - Chan,Angelo H C, AU - Sanders,Kate, AU - Ali,Syed A, AU - Hendrikx,Iwan, AU - Dunstan,Nathan, AU - Fry,Bryan G, Y1 - 2013/12/18/ PY - 2013/09/14/received PY - 2013/12/13/revised PY - 2013/12/16/accepted PY - 2013/12/20/entrez PY - 2013/12/20/pubmed PY - 2014/9/12/medline SP - 2621 EP - 55 JF - Toxins JO - Toxins (Basel) VL - 5 IS - 12 N2 - 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. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/24351719/Venom_down_under:_dynamic_evolution_of_Australian_elapid_snake_toxins_ L2 - http://www.mdpi.com/resolver?pii=toxins5122621 DB - PRIME DP - Unbound Medicine ER -