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Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet.

ABSTRACT: BACKGROUND:The relative influence of diet and phylogeny on snake venom activity is a poorly understood aspect of snake venom evolution. We measured the activity of two enzyme toxin groups - phospholipase A2 (PLA2), and L-amino acid oxidase (LAAO) - in the venom of 39 species of Australian elapids (40% of terrestrial species diversity) and used linear parsimony and BayesTraits to investigate any correlation between enzyme activity and phylogeny or diet. RESULTS:PLA2 activity ranged from 0 to 481?nmol/min/mg of venom, and LAAO activity ranged from 0 to 351?nmol/min/mg. Phylogenetic comparative methods, implemented in BayesTraits showed that enzyme activity was strongly correlated with phylogeny, more so for LAAO activity. For example, LAAO activity was absent in both the Vermicella and Pseudonaja/Oxyuranus clade, supporting previously proposed relationships among these disparate taxa. There was no association between broad dietary categories and either enzyme activity. There was strong evidence for faster initial rates of change over evolutionary time for LAAO (delta parameter mean 0.2), but no such pattern in PLA2 (delta parameter mean 0.64). There were some exceptions to the phylogenetic patterns of enzyme activity: different PLA2 activity in the ecologically similar sister-species Denisonia devisi and D. maculata; large inter-specific differences in PLA2 activity in Hoplocephalus and Austrelaps. CONCLUSIONS:We have shown that phylogeny is a stronger influence on venom enzyme activity than diet for two of the four major enzyme families present in snake venoms. PLA2 and LAAO activities had contrasting evolutionary dynamics with the higher delta value for PLA2 Some species/individuals lacked activity in one protein family suggesting that the loss of single protein family may not incur a significant fitness cost.

SUBMITTER: Tasoulis T

PROVIDER: S-EPMC6958663 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet.

Tasoulis Theo T Lee Michael S Y MSY Ziajko Manon M Dunstan Nathan N Sumner Joanna J Isbister Geoffrey K GK

BMC evolutionary biology 20200113 1

<h4>Background</h4>The relative influence of diet and phylogeny on snake venom activity is a poorly understood aspect of snake venom evolution. We measured the activity of two enzyme toxin groups - phospholipase A<sub>2</sub> (PLA<sub>2</sub>), and L-amino acid oxidase (LAAO) - in the venom of 39 species of Australian elapids (40% of terrestrial species diversity) and used linear parsimony and BayesTraits to investigate any correlation between enzyme activity and phylogeny or diet.<h4>Results</h ...[more]

PMID: 31931699

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Project description:Some Australian elapids possess potently procoagulant coagulotoxic venoms which activate the zymogen prothrombin into the functional enzyme thrombin. Although the activity of Australian elapid prothrombin-activators has been heavily investigated with respect to the mammalian, and in particular, human clotting cascades, very few studies have investigated the activity of their venom upon reptile plasmas. This is despite lizards representing both the primary diet of most Australian elapids and also representing natural predators. This study investigated the procoagulant actions of a diverse range of Australian elapid species upon plasma from known prey species within the genera Tiliqua (blue tongue skinks) as well as known predator species within the genera Varanus (monitor lizards). In addition to identifying significant variation in the natural responses of the coagulation cascade between species from the genera Tiliqua and Varanus relative to each other, as well as other vertebrate lineages, notable differences in venom activity were also observed. Within the genus Tiliqua, both T. rugosa and T. scincoides plasma displayed significant resistance to the procoagulant activity of Pseudechis porphyriacus venom, despite being susceptible to all other procoagulant elapid venoms. These results indicate that T. rugosa and T. scincoides have evolved resistance within their plasma to the coagulotoxic venom activity of the sympatric species P. porphyriacus. Other venoms were able to activate Tiliqua prothrombin, which suggests that the lessened activity of P. porphyriacus venom is not due to modifications of the prothrombin and may instead be due to a serum factor that specifically binds to P. porphyriacus toxins, as has been previously seen for squirrels resistant to rattlesnake venom. In contrast, none of the predatory lizards studied (Varanus giganteus, V. mertensi and V. varius) demonstrated resistance to the venom. This suggests that the mechanical protection afforded by thick osteodermic scales, and prey handling behaviour, removes a selection pressure for the evolution of resistance in these large predatory lizards. These results therefore reveal differential interactions between venoms of snakes with sympatric lizards that are on opposite sides of the predator-prey arms race.

Project description:This review describes the research aimed at the development of universal antivenom against elapid neurotoxic snake venoms. The antivenoms produced in Thailand in the 1980s were of low potency, especially against the elapid venoms. This was thought to be due to the low immunogenicity of the α-neurotoxins, which are the most lethal toxins in these venoms. Comparisons of various α-neurotoxin conjugates and polymers, and also different immunological adjuvants, showed that the adjuvant used is the major determinant in the antibody response in horses. The potent Freund's adjuvant was not used due to its severe local side-effect in horses. Therefore, a novel immunization protocol termed 'low dose, low volume multi-site' was developed for use in horses. This immunization protocol has led to the production of highly potent monospecific antivenoms against several elapid and viperid venoms, and two potent polyspecific antivenoms, one against 4 neurotoxic and another against 3 hematotoxic venoms. The immunization protocol has also led to other improvements in antivenom production including: several fold increases in antiserum potency, a reduction in the time required to reach therapeutically useful antibody titers, a 90% reduction in the amount of venom used, and 100% of the horses responding to the immunization program. This development is partly responsible for significant decrease in the Thailand's annual snakebite death toll from a few dozens to mostly nil in recent years. Finally, a simple and novel immunization strategy, using a 'diverse toxin repertoire' composed of numerous elapid toxin fractions as immunogen, was proposed and tested. This immunization procedure has resulted in the successful production of a widely paraspecific antiserum against at least 36 neurotoxic venoms of 28 species encompassing 10 genera and from 20 countries on four continents, and possibly against all elapid venoms with α-neurotoxins as the lethal toxins. These results indicate that, with optimizations of the composition of the 'diverse toxin repertoire', the immunization scheme and antibody fractionation to increase the antivenom neutralizing potency, an effective universal antivenom against the neurotoxic elapid snakes of the world can be produced.

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Project description:BackgroundVenom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulatory investigations in elapid snakes have been limited. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis- and trans-acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris).ResultsAlthough there is conservation in high-level mechanistic pathways regulating venom production (unfolded protein response, Notch signaling and cholesterol homeostasis), there are differences in the regulation of histone methylation enzymes, transcription factors, and microRNAs in venom glands from these two snake families. Histone methyltransferases and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland in comparison to the viperids, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. The presence of Sp1 binding sites across multiple elapid toxin gene promoter regions that have been experimentally determined to regulate expression, in addition to upregulation of Sp1 after venom milking, suggests this transcription factor is involved in elapid toxin expression. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target a diversity of toxin transcripts in the elapid P. textilis venom gland, but only snake venom metalloproteinase transcripts in the viperid C. viridis venom gland. These results suggest differences in toxin gene posttranscriptional regulation between the elapid P. textilis and viperid C. viridis.ConclusionsOur comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin regulation between these two snake families, demonstrating multiple different regulatory mechanisms underpin a venomous phenotype.

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Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet.

Publications

Activity of two key toxin groups in Australian elapid venoms show a strong correlation to phylogeny but not to diet.

Similar Datasets

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