Unique physiological and regulatory activity drives divergent toxin and non-toxin gene expression in rattlesnake accessory venom glands.

Understanding the mechanisms by which organs and tissues evolve new physiological functions is central to understanding the evolution of novelty. This is particularly interesting in the context of related tissues that evolve specialized, yet complementary, functions. Snake venom glands are an attractive system to test hypotheses related to the evolution and specialization of novel physiological function, as these modified salivary glands have evolved over ∼60 MY to synthesize and store venom.

Discerning specific thrombolytic activities and blood clot degradomes of diverse snake venoms with untargeted peptidomics.

Background: Many snake venoms have been shown to possess thrombolytic activity. However, it remains unclear if actions on other clot-stabilizing proteins beyond fibrin chains contribute significantly to venom-induced thrombolysis because the clot-wide targets of venom proteases and the mechanisms responsible for thrombolysis are not well understood.

Objectives: Here, we utilized a high-throughput, time-based thrombolysis assay in combination with untargeted peptidomics to provide comprehensive insight into the effects of venom from 5 snake species on blood clot degradation.

Disentangling a genome-wide mosaic of conflicting phylogenetic signals in Western Rattlesnakes.

Species tree inference is often assumed to be more accurate as datasets increase in size, with whole genomes representing the best-case-scenario for estimating a single, most-likely speciation history with high confidence. However, genomes may harbor a complex mixture of evolutionary histories among loci, which amplifies the opportunity for model misspecification and impacts phylogenetic inference. Accordingly, multiple distinct and well-supported phylogenetic trees are often recovered from genome-scale data, and approaches for biologically interpreting these distinct signatures are a major challenge for evolutionary biology in the age of genomics.

Venom variation and ontogenetic changes in the Crotalus molossus complex: Insights into composition, activities, and antivenom neutralization.

The Crotalus molossus complex consists of five to seven phylogenetically related lineages of black-tailed rattlesnakes widely distributed in Mexico. While previous studies have noted venom variation within specific lineages of the Crotalus molossus complex, a comprehensive characterization of interspecific and ontogenetic venom variations, their functional implications, and the neutralizing ability of the Mexican antivenom against these variants remains largely unexamined. Herein, using two proteomic approaches for five lineages (C.

Diverse Gene Regulatory Mechanisms Alter Rattlesnake Venom Gene Expression at Fine Evolutionary Scales.

Understanding and predicting the relationships between genotype and phenotype is often challenging, largely due to the complex nature of eukaryotic gene regulation. A step towards this goal is to map how phenotypic diversity evolves through genomic changes that modify gene regulatory interactions. Using the Prairie Rattlesnake (Crotalus viridis) and related species, we integrate mRNA-seq, proteomic, ATAC-seq and whole-genome resequencing data to understand how specific evolutionary modifications to gene regulatory network components produce differences in venom gene expression.

Assessing Target Specificity of the Small Molecule Inhibitor MARIMASTAT to Snake Venom Toxins: A Novel Application of Thermal Proteome Profiling.

New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide.

A plethora of rodents: Rattlesnake predators generate unanticipated patterns of venom resistance in a grassland ecosystem.

Predation has the potential to impart strong selective pressures on organisms within their environments, resulting in adaptive changes in prey that minimize risk of predation. Pressures from venomous snakes present an exceptional challenge to prey, as venom represents a unique chemical arsenal evolutionarily tailored to incapacitate prey. In response, venom resistance has been detected in various snake prey species, and to varying degrees.

The best of both worlds? Rattlesnake hybrid zones generate complex combinations of divergent venom phenotypes that retain high toxicity.

Studying the consequences of hybridization between closely related species with divergent traits can reveal patterns of evolution that shape and maintain extreme trophic adaptations. Snake venoms are an excellent model system for examining the evolutionary and ecological patterns that underlie highly selected polymorphic traits. Here we investigate hybrid venom phenotypes that result from natural introgression between two rattlesnake species that express highly divergent venom phenotypes: Crotalus o.

Snakes on a plain: biotic and abiotic factors determine venom compositional variation in a wide-ranging generalist rattlesnake.

Background: Snake 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.

Evidence that genomic incompatibilities and other multilocus processes impact hybrid fitness in a rattlesnake hybrid zone.

Hybrid zones provide valuable opportunities to understand the genomic mechanisms that promote speciation by providing insight into factors involved in intermediate stages of speciation. Here, we investigate introgression in a hybrid zone between two rattlesnake species (Crotalus viridis and Crotalus oreganus concolor) that have undergone historical allopatric divergence and recent range expansion and secondary contact. We use Bayesian genomic cline models to characterize genomic patterns of introgression between these lineages and identify loci potentially subject to selection in hybrids.

The roles of balancing selection and recombination in the evolution of rattlesnake venom.

The origin of snake venom involved duplication and recruitment of non-venom genes into venom systems. Several studies have predicted that directional positive selection has governed this process. Venom composition varies substantially across snake species and venom phenotypes are locally adapted to prey, leading to coevolutionary interactions between predator and prey.

Origins, genomic structure and copy number variation of snake venom myotoxins.

Crotamine, myotoxin a and homologs are short peptides that often comprise major fractions of rattlesnake venoms and have been extensively studied for their bioactive properties. These toxins are thought to be important for rapidly immobilizing mammalian prey and are implicated in serious, and sometimes fatal, responses to envenomation in humans. While high quality reference genomes for multiple venomous snakes are available, the loci that encode myotoxins have not been successfully assembled in any existing genome assembly.

Snake venom gene expression is coordinated by novel regulatory architecture and the integration of multiple co-opted vertebrate pathways.

Understanding how regulatory mechanisms evolve is critical for understanding the processes that give rise to novel phenotypes. Snake venom systems represent a valuable and tractable model for testing hypotheses related to the evolution of novel regulatory networks, yet the regulatory mechanisms underlying venom production remain poorly understood. Here, we use functional genomics approaches to investigate venom regulatory architecture in the prairie rattlesnake and identify -regulatory sequences (enhancers and promoters), -regulatory transcription factors, and integrated signaling cascades involved in the regulation of snake venom genes.

Asymmetrical expression of toxins between the left and right venom glands of an individual prairie rattlesnake (Crotalus viridis viridis).

It is assumed that toxin expression is equivalent between left and right glands of a single snake. In the current study, we report venoms that differ in enzyme functionality and overall composition between the left and right gland of a single snake. The right gland produced venom of comparable composition to venom previously extracted from the same individual; however, the left gland produced venom with overall lower protein content and considerably less enzyme activity.

Crotalus oreganus concolor: Envenomation Case with Venom Analysis and a Diagnostic Conundrum of Myoneurologic Symptoms.

A case of midget-faded rattlesnake (Crotalus oreganus concolor) envenomation of an adult male professional herpetologist occurred in a rural setting and resulted in an array of venom induced myoneurologic symptoms. The patient experienced blurry vision, total body paresthesia, dyspnea, chest tightness, and waves of spastic muscle movements of the hands and feet that resembled tetany. It was not apparent whether these symptoms were potentially venom induced or were related to stress-induced physiologic responses.

The origins and evolution of chromosomes, dosage compensation, and mechanisms underlying venom regulation in snakes.

Here we use a chromosome-level genome assembly of a prairie rattlesnake (), together with Hi-C, RNA-seq, and whole-genome resequencing data, to study key features of genome biology and evolution in reptiles. We identify the rattlesnake Z Chromosome, including the recombining pseudoautosomal region, and find evidence for partial dosage compensation driven by an evolutionary accumulation of a female-biased up-regulation mechanism. Comparative analyses with other amniotes provide new insight into the origins, structure, and function of reptile microchromosomes, which we demonstrate have markedly different structure and function compared to macrochromosomes.

Evidence for divergent patterns of local selection driving venom variation in Mojave Rattlesnakes (Crotalus scutulatus).

Snake venoms represent an enriched system for investigating the evolutionary processes that lead to complex and dynamic trophic adaptations. It has long been hypothesized that natural selection may drive geographic variation in venom composition, yet previous studies have lacked the population genetic context to examine these patterns. We leverage range-wide sampling of Mojave Rattlesnakes (Crotalus scutulatus) and use a combination of venom, morphological, phylogenetic, population genetic, and environmental data to characterize the striking dichotomy of neurotoxic (Type A) and hemorrhagic (Type B) venoms throughout the range of this species.

DNA barcodes from snake venom: a broadly applicable method for extraction of DNA from snake venoms.

DNA barcoding is a simple technique used to develop a large-scale system of classification that is broadly applicable across a wide variety of taxa. DNA-based analysis of snake venoms can provide a system of classification independent of currently accepted taxonomic relationships by generating DNA barcodes specific to each venom sample. DNA purification from dried snake venoms has previously required large amounts of starting material, has resulted in low yields and inconsistent amplification, and was possible with front-fanged snakes only.

First reported case of thrombocytopenia from a Heterodon nasicus envenomation.

Context: The vast majority of the 2.5 million annual worldwide venomous snakebites are attributed to Viperidae or Elapidae envenomations. Of the nearly 2000 Colubridae species described, only a handful are known to cause medically significant envenomations.

The effects of hybridization on divergent venom phenotypes: Characterization of venom from Crotalus scutulatus scutulatus × Crotalus oreganus helleri hybrids.

Hybridization between divergent species can be analyzed to elucidate expression patterns of distinct parental characteristics, as well as to provide information about the extent of reproductive isolation between species. A known hybrid cross between two rattlesnakes with highly divergent venom phenotypes provided the opportunity to examine occurrence of parental venom characteristics in the F1 hybrids as well as ontogenetic shifts in the expression of these characters as the hybrids aged. Although venom phenotypes of adult rattlesnake venoms are known for many species, the effect of hybridization on phenotype inheritance is not well understood, and effects of hybridization on venom ontogeny have not yet been investigated.