Highly Evolvable: Investigating Interspecific and Intraspecific Venom Variation in Taipans (Oxyuranus spp.) and Brown Snakes (Pseudonaja spp.)

Thiel, Jory van; Alonso, Luis L.; Slagboom, Julien; Dunstan, Nathan; Wouters, Roel M.; Modahl, Cassandra M.; Vonk, Freek J.; Jackson, Timothy N. W.; Kool, Jeroen

doi:10.3390/toxins15010074

Cited by 16 publications

(19 citation statements)

References 49 publications

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“…The scope of our study was on interspecific relationships between venom complexity and diet diversity, such that by controlling for intraspecific variation, we consider macroevolutionary patterns of venom evolution rather than relationships between populations within a species. Although intraspecific studies of venom variation are vital to our understanding of venom evolution [2,28], our study has a different focus and cannot address questions related to how individual snake venoms are related to the diets of individual snakes.…”

Section: Discussionmentioning

confidence: 99%

Diversity Begets Diversity When Diet Drives Snake Venom Evolution, but Evenness Rather Than Richness Is What Counts

Schaeffer

Pascolutti

Jackson

et al. 2023

Toxins

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Snake venoms are primarily used to subjugate prey, and consequently, their evolution has been shown to be predominantly driven by diet-related selection pressure. Venoms tend to be more lethal to prey than non-prey species (except in cases of toxin resistance), prey-specific toxins have been identified, and preliminary work has demonstrated an association between the diversity of diet classes and that of toxicological activities of whole venom. However, venoms are complex mixtures of many toxins, and it remains unclear how toxin diversity is driven by diet. Prey-specific toxins do not encompass the molecular diversity of venoms, and whole venom effects could be driven by one, few, or all components, so the link between diet and venom diversity remains minimally understood. Here, we collated a database of venom composition and diet records and used a combination of phylogenetic comparative methods and two quantitative diversity indices to investigate whether and how diet diversity relates to the toxin diversity of snake venoms. We reveal that venom diversity is negatively related to diet diversity using Shannon’s index but positively related using Simpson’s index. Since Shannon’s index predominantly considers the number of prey/toxins, whereas Simpson’s index more strongly reflects evenness, we provide insights into how the diet–venom diversity link is driven. Specifically, species with low diet diversity tend to have venoms dominated by a few abundant (possibly specialised) toxin families, whereas species with diverse diets tend to ‘hedge their bets’ by having venoms with a more even composition of different toxin classes.

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Section: Discussionmentioning

confidence: 99%

Diversity Begets Diversity When Diet Drives Snake Venom Evolution, but Evenness Rather Than Richness Is What Counts

Schaeffer

Pascolutti

Jackson

et al. 2023

Toxins

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“…Venom variation in snakes can be observed on the interspecific level (between species) and intraspecific level (within a species) [ 9 ]. While venom variation between species has been well studied (e.g., [ 4 , 5 , 10 , 11 ]), the extent of intraspecific variation is starting to gain significant attention [ 12 ]. A thorough understanding of venom variation is of interest to different scientific disciplines, as venom variation provides a model system for understanding adaptive responses to biotic and abiotic factors in an ecological context [ 5 , 7 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…The current main drawback in this analytical workflow is the tedious manual integration of all peak areas found in each venom analysed. In one of our previous studies, a similar workflow was demonstrated with venoms of Australian elapids for which the LC-MS data was indeed labouriously integrated manually (and the HT venomics results were not included) [ 10 ]. This drawback of manually integrating the intensities of all toxin m / z values found for each venom (and in this endeavour, only considering the highest charge state per toxin) is illustrated by the many months it took to process all LC-MS data.…”

Section: Introductionmentioning

confidence: 99%

“…Our dataset covers all twelve documented species of this monophyletic clade, including several widespread localities. The LC-MS dataset was taken from our previous study, where the LC-MS data were manually integrated and processed [ 10 ]. This was carried out to validate the automatic data extraction procedure presented in the current study with the previous manual peak area integration [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Studying Venom Toxin Variation Using Accurate Masses from Liquid Chromatography–Mass Spectrometry Coupled with Bioinformatic Tools

Alonso,

van Thiel,

Slagboom

et al. 2024

Toxins

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This study provides a new methodology for the rapid analysis of numerous venom samples in an automated fashion. Here, we use LC-MS (Liquid Chromatography–Mass Spectrometry) for venom separation and toxin analysis at the accurate mass level combined with new in-house written bioinformatic scripts to obtain high-throughput results. This analytical methodology was validated using 31 venoms from all members of a monophyletic clade of Australian elapids: brown snakes (Pseudonaja spp.) and taipans (Oxyuranus spp.). In a previous study, we revealed extensive venom variation within this clade, but the data was manually processed and MS peaks were integrated into a time-consuming and labour-intensive approach. By comparing the manual approach to our new automated approach, we now present a faster and more efficient pipeline for analysing venom variation. Pooled venom separations with post-column toxin fractionations were performed for subsequent high-throughput venomics to obtain toxin IDs correlating to accurate masses for all fractionated toxins. This workflow adds another dimension to the field of venom analysis by providing opportunities to rapidly perform in-depth studies on venom variation. Our pipeline opens new possibilities for studying animal venoms as evolutionary model systems and investigating venom variation to aid in the development of better antivenoms.

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“…Pseudonaja textilis is the second most lethal terrestrial venomous snake in the world, based upon murine models of toxicity (Broad et al 1979), and is responsible for the majority of snakebite deaths in eastern Australia (Sutherland 1992; White 2009). Venom gland transcriptomics and venom proteomics have been used to profile P. textilis venom composition (Birrell et al 2006; Viala et al 2015; Reeks et al 2016), and studies have documented geographic, seasonal, ontogenetic, and individual venom variation (Williams and White 1992; Flight et al 2006; Skejić and Hodgson 2013; Skejić et al 2015; Jackson et al 2016; McCleary et al 2016; van Thiel et al 2023). Using high-throughput transcriptomics, we evaluated P. textilis mRNAs and microRNAs (miRNAs) in a Milked Venom Gland (MVG) and Unmilked Venom Gland (UVG) from an individual snake, eliminating contributing factors involved in venom variation, to identify mechanisms regulating toxin expression.…”

Section: Introductionmentioning

confidence: 99%

Distinct regulatory networks control toxin gene expression in elapid and viperid snakes

Modahl

Han

Thiel

et al. 2023

Preprint

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Venom 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 regulation in elapids is largely unexplored. 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). Although there is conservation in high-level mechanistic pathways regulating venom production, there are histone methylation, transcription factor, and microRNA regulatory differences between these two snake families. Histone methyltransferases (KMT2A, KMT2C and KMT2D) and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland, 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. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target different toxin transcripts. Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin evolution between these two snake families, demonstrating multiple toxin genes and regulatory mechanisms converged to underpin a highly venomous phenotype.

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Highly Evolvable: Investigating Interspecific and Intraspecific Venom Variation in Taipans (Oxyuranus spp.) and Brown Snakes (Pseudonaja spp.)

Cited by 16 publications

References 49 publications

Diversity Begets Diversity When Diet Drives Snake Venom Evolution, but Evenness Rather Than Richness Is What Counts

Diversity Begets Diversity When Diet Drives Snake Venom Evolution, but Evenness Rather Than Richness Is What Counts

Studying Venom Toxin Variation Using Accurate Masses from Liquid Chromatography–Mass Spectrometry Coupled with Bioinformatic Tools

Distinct regulatory networks control toxin gene expression in elapid and viperid snakes

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