Snakes on a Plain: Complex Biotic and Abiotic Factors Determine Venom Variation in North America's Widest Ranging Rattlesnake
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Crotalus Viridis (ncbitaxon:8739)
SUBMITTER: 
Kirk Hansen
PROVIDER: MSV000089601 | MassIVE | Fri Jun 03 13:40:00 BST 2022
SECONDARY ACCESSION(S): PXD034274
REPOSITORIES: MassIVE
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Project description:BackgroundSnake venoms are trophic adaptations that represent an ideal model to examine the evolutionary factors that shape polymorphic traits under strong natural selection. Venom compositional variation is substantial within and among venomous snake species. However, the forces shaping this phenotypic complexity, as well as the potential integrated roles of biotic and abiotic factors, have received little attention. Here, we investigate geographic variation in venom composition in a wide-ranging rattlesnake (Crotalus viridis viridis) and contextualize this variation by investigating dietary, phylogenetic, and environmental variables that covary with venom.ResultsUsing shotgun proteomics, venom biochemical profiling, and lethality assays, we identify 2 distinct divergent phenotypes that characterize major axes of venom variation in this species: a myotoxin-rich phenotype and a snake venom metalloprotease (SVMP)-rich phenotype. We find that dietary availability and temperature-related abiotic factors are correlated with geographic trends in venom composition.ConclusionsOur findings highlight the potential for snake venoms to vary extensively within species, for this variation to be driven by biotic and abiotic factors, and for the importance of integrating biotic and abiotic variation for understanding complex trait evolution. Links between venom variation and variation in biotic and abiotic factors indicate that venom variation likely results from substantial geographic variation in selection regimes that determine the efficacy of venom phenotypes across populations and snake species. Our results highlight the cascading influence of abiotic factors on biotic factors that ultimately shape venom phenotype, providing evidence for a central role of local selection as a key driver of venom variation.
| S-EPMC10246093 | biostudies-literature
Project description:The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117–1202 μM). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.
2024-01-10 | GSE221799 | GEO
Project description:Snakebite is a major public health concern in many parts of the world, including India, where over 58,000 deaths occur annually due to this highly neglected tropical disease. The common krait (Bungarus caeruleus), one of the ‘big four’ Indian snakes, is responsible for the second-highest number of snakebite-related deaths in the country. The venom protein composition of common krait venoms from different locations were investigated. Venoms were pre-fractionated using RP-HPLC and SDS-PAGE, and subjected to mass spectromentry analysis. The relative abundance of each toxin family was estimated and compared across different locations.
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Project description:Pathological and inflammatory events in muscle after injection of snake venoms vary in different regions of the affected tissue and at different time intervals. In order to study such heterogeneity in the immune cell microenvironment, a murine model of muscle necrosis based on the injection of the venom of Daboia russelii was used.
2023-03-07 | GSE222977 | GEO
Project description:Latest advancement of omics technologies allows in-depth characterization of venom compositions. In the present work we present a proteomic study of two snake venoms of the genus Naja i.e. Naja naja (black cobra) and Naja oxiana (brown cobra), of Pakistani origin. The present study has shown that these snake venoms consist of a highly diversified proteome. Furthermore, the data also revealed variation among closely related species. High throughput mass spectrometric analysis of the venom proteome allowed to identify for the N. naja venom 34 protein families and for the N. oxiana 24 protein families. The comparative evaluation of the two venoms showed that N. naja consists of a more complex venom proteome than N. oxiana venom.
2020-10-29 | PXD018726 | Pride
Project description:When one phenotype is not enough – divergent evolutionary trajectories govern venom variation in a widespread rattlesnake species
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Project description:Snake venoms contain complex mixtures of proteins that play vital roles in the survival of venomous snakes. In line with their diverse pharmacological activities, the protein compositions of snake venoms can be highly variable, and efforts to characterise the primary structures of such proteins are extensive and ongoing. In addition, a significant knowledge gap exists in terms of higher-order interactionsbetweenproteinsproposedto modulate venom potency, which poses a challenge for treatment of envenomation and development of successful therapeutic applications.Here we use a multifaceted mass spectrometrybased approach to characteriseproteinsfrom the medically significant venomsof Collett’s snake Pseudechis collettiand the puff adder Bitis arietans.Following chromatographic fractionation and bottom-up proteomics identification, native mass spectrometry identified, among other components, a 117 kDa non-covalent L-amino acid oxidase dimer in the P. collettivenom and a 60 kDa C-type lectin tetramer in the B. arietansvenom. Furthermore, a 27.7 kDa covalently-linked phospholipase A2(PLA2) dimer was identified in P. collettivenom, and thePLA2species were shownto adopt a highly compact geometry based on ion mobility measurements. Exploration of the catalytic efficiencies of the monomeric and dimeric forms of PLA2revealed that the dimeric PLA2 possessed greater bioactivity than the monomeric PLA2s.This work contributes to ongoing efforts to catalogue the protein components of snake venoms, and notably,itemphasises the importance of understanding higher-order protein interactions in venomsand the utility of a combined mass spectrometric approachfor this task.
2020-02-17 | PXD016503 | Pride
Project description:Protein expression is a major link in the genotype-phenotype relationship, and processes affecting protein abundances, such as rates of transcription and translation, could contribute to phenotypic evolution if they generate heritable variation. Recent work has suggested that mRNA abundances do not accurately predict final protein abundances, which would imply that post-transcriptional regulatory processes contribute significantly to phenotypes. Post-transcriptional processes also appear to buffer changes in transcriptional patterns as species diverge, suggesting that the transcriptional changes have little or no effect on the phenotypes under study. We tested for concordance between mRNA and protein expression levels in snake venoms by means of mRNA-seq and quantitative mass spectrometry for 11 snakes representing 10 species, six genera, and three families. In contrast to most previous work, we found high correlations between venom-gland transcriptomes and venom proteomes for ten of our 11 comparisons. We tested for protein-level buffering of transcriptional changes during species divergence by comparing the difference between transcript abundance and protein abundance for three pairs of species and one intraspecific pair. We found no evidence for buffering during divergence of our three species pairs but did find evidence for protein-level buffering for our single intraspecific comparison, suggesting that buffering, if present, was a transient phenomenon in venom divergence. Our results demonstrated that post-transcriptional mechanisms did not contribute significantly to phenotypic evolution in venoms and suggest a more prominent and direct role for cis-regulatory evolution in phenotypic variation, particularly for snake venoms.
2015-11-09 | PXD002837 | Pride
Project description:Snakebite affects ~1.8 million people annually. The current standard of care are antibody-based antivenoms, which are difficult to access and are not effective against local tissue injury, the primary cause of morbidity. Here we use a functional genomics approach to define human genes that genetically interact with spitting cobra venoms. Most genes that confer resistance to venom cytotoxicity control proteoglycan biosynthesis, suggesting heparinoids as possible inhibitors. Here we show that heparinoids prevent venom cytotoxicity by inhibiting three-finger cytotoxins. Critically, the FDA-approved heparinoid tinzaparin was found to reduce tissue damage in vivo when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom mechanisms provides new insight into how we can treat cobra bites, information that can help improve the lives of millions of people worldwide.
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