Phenotypic Variation in Mojave Rattlesnake (Crotalus scutulatus) Venom Is Driven by Four Toxin Families

Strickland, Jason L.; Mason, Andrew J.; Rokyta, Darin R.; Parkinson, Christopher L.

doi:10.3390/toxins10040135

Cited by 34 publications

(31 citation statements)

References 61 publications

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“…1, Table 1). The number of recovered toxins and recovered families were generally consistent with those of other viperid transcriptomes [25,[34][35][36][37] and with estimates of toxin family size in early high-throughput transcriptomes of B. schlegelii and B. lateralis [38] (Table 2, Table 3).…”

Section: Transcriptome Characterizationsupporting

confidence: 70%

Trait differentiation and modular toxin expression in palm-pitvipers

et al. 2020

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Background: Modularity is the tendency for systems to organize into semi-independent units and can be a key to the evolution and diversification of complex biological systems. Snake venoms are highly variable modular systems that exhibit extreme diversification even across very short time scales. One well-studied venom phenotype dichotomy is a trade-off between neurotoxicity versus hemotoxicity that occurs through the high expression of a heterodimeric neurotoxic phospholipase A 2 (PLA 2 ) or snake venom metalloproteinases (SVMPs). We tested whether the variation in these venom phenotypes could occur via variation in regulatory sub-modules through comparative venom gland transcriptomics of representative Black-Speckled Palm-Pitvipers (Bothriechis nigroviridis) and Talamancan Palm-Pitvipers (B. nubestris). Results: We assembled 1517 coding sequences, including 43 toxins for B. nigroviridis and 1787 coding sequences including 42 toxins for B. nubestris. The venom gland transcriptomes were extremely divergent between these two species with one B. nigroviridis exhibiting a primarily neurotoxic pattern of expression, both B. nubestris expressing primarily hemorrhagic toxins, and a second B. nigroviridis exhibiting a mixed expression phenotype. Weighted gene coexpression analyses identified six submodules of transcript expression variation, one of which was highly associated with SVMPs and a second which contained both subunits of the neurotoxic PLA 2 complex. The sub-module association of these toxins suggest common regulatory pathways underlie the variation in their expression and is consistent with known patterns of inheritance of similar haplotypes in other species. We also find evidence that module associated toxin families show fewer gene duplications and transcript losses between species, but module association did not appear to affect sequence diversification. Conclusion: Sub-modular regulation of expression likely contributes to the diversification of venom phenotypes within and among species and underscores the role of modularity in facilitating rapid evolution of complex traits.

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Section: Transcriptome Characterizationsupporting

confidence: 70%

Trait differentiation and modular toxin expression in palm-pitvipers

et al. 2020

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“…2). Similar toxin-specific strategies have been observed between 243 populations of snakes, but we show that the trend extends phylogenetically to different species 244 as well as different families (39,40). While individual venom components do exhibit significant 245 phylogenetic inertia ( Fig.…”

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confidence: 70%

Many options, few solutions: over 60 million years snakes converged on a few optimal venom formulations

Barua

Mikheyev

2018

Preprint

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Gene expression changes contribute to complex trait variations in both individuals and populations. However, how gene expression influences changes of complex traits over macroevolutionary timescales remains poorly understood. Being comprised of proteinaceous cocktails, snake venoms are unique in that the expression of each toxin can be quantified and mapped to a distinct genomic locus and traced for millions of years. Using a phylogenetic generalized linear mixed model, we analysed expression data of toxin genes from 52 snake species spanning the three venomous snake families, and estimated phylogenetic covariance, which acts as a measure of evolutionary constraint. We find that evolution of toxin combinations is not constrained. However, while all combinations are in principle possible, the actual dimensionality of phylomorphic space is low, with envenomation strategies focused around only four major toxins: metalloproteases, three-finger toxins, serine proteases, and phospholipases A2. While most extant snakes prioritize either a single or a combination of major toxins, they are repeatedly recruited and lost. We find that over macroevolutionary timescales the venom phenotypes were not shaped by phylogenetic constraints, which include important microevolutionary constraints such as epistasis and pleiotropy, but more likely by ecological filtering that permits a few optimal solutions. As a result, phenotypic optima were repeatedly attained by distantly related species. These results indicate that venoms evolve by selection on biochemistry of prey envenomation, which permit diversity though parallelism and impose strong limits, since only a few of the theoretically possible strategies seem to work well and are observed in extant snakes.

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“…Both types seem randomly distributed across the phylogeny of rattlesnakes, and sometimes co-occur within populations of a single species. The Mohave rattlesnake, Crotalus scutulatus , is well-known for displaying both venom strategies across a continuous distributional range in the North American deserts (Figure 1A) [11-13]. This species thus represents an ideal system to investigate the evolutionary processes and molecular mechanisms shaping intraspecific phenotypic variation and adaptation within a common genetic background.…”

Section: Resultsmentioning

confidence: 99%

“…Because the primary function of venom in snakes is the acquisition of prey ( 9 ], adaptation to specific diet, or local prey communities is generally invoked as the foremost driver of venom evolution [13, 15, 22-24], and has become the dominant paradigm in the study of snake venom evolution. Since even subtle intraspecific variation in venom composition can reflect selection for local prey [24, 25], we hypothesized that the stark contrast in toxicity and mode of action (neurotoxic vs. haemorrhagic) between A and B venoms in C. scutulatus would have a significant impact on the snakes’ foraging biology.…”

Section: Resultsmentioning

confidence: 99%

“…Intermediate A+B venoms containing both SVMPs and MTX are found at the contact zones between the two venom types. Besides SVMPs and the neurotoxic PLA2, additional toxins belonging to different gene families show geographic variation in their expression, in particular myotoxin, a potent voltage-gated potassium channel inhibitor which causes rapid paralysis and muscle necrosis [12, 13].…”

Section: Methodsmentioning

confidence: 99%

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When one phenotype is not enough – divergent evolutionary trajectories govern venom variation in a widespread rattlesnake species

Zancolli

Calvete

Cardwell

et al. 2018

Preprint

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32 33 2 SUMMARY 34Understanding the relationship between genome, phenotypic variation, and the ecological 35 pressures that act to maintain that variation, represents a fundamental challenge in evolutionary 36 biology. Functional polymorphisms typically segregate in spatially isolated populations [1, 2] 37 and/or discrete ecological conditions [3][4][5], whereas dissecting the evolutionary processes 38 involved in adaptive geographic variation across a continuous spatial distribution is much more 39 challenging [6]. Additionally, pleiotropic interactions between genes and phenotype often 40 complicate the identification of specific genotype-phenotype links [7][8], and thus of the selective 41 pressures acting on them. Animal venoms are ideal systems to overcome these constraints: they 42 are complex and variable, yet easily quantifiable molecular phenotypes with a clear function and 43 a direct link to both genome and fitness [9]. Here, we use dense and widespread population-level 44 sampling of the Mohave rattlesnake, Crotalus scutulatus, and show that genomic structural 45 variation at multiple loci underlies extreme geographic variation in venom composition, which is 46 maintained despite extensive gene flow. Unexpectedly, selection for diet does not explain venom 47 variation, contrary to the dominant paradigm of venom evolution, and neither does neutral 48 population structure caused by past vicariance. Instead, different toxin genes correlate with 49 distinct environmental factors, suggesting that divergent selective pressures can act on individual 50 loci independently of their genomic proximity or co-expression patterns. Local-scale spatial 51 heterogeneity thus appears to maintain a remarkably ancient complex of molecular phenotypes, 52 which have been retained in populations that diverged more than 1.5-2 MYA, representing an 53 exceptional case of long-term structural polymorphism. These results emphasize how the 54 interplay between genomic architecture and spatial heterogeneity in selective pressures may 55 facilitate the retention of functional polymorphisms of an adaptive phenotype. 57 RESULTS AND DISCUSSION58 Rattlesnake (Crotalus) venoms are among the most complex exocrine secretions in nature, with 59 tens to hundreds of individual components. They display a puzzling phenotypic dichotomy, with 60 two largely mutually exclusive venom strategies: highly lethal type A venoms, characterized by 61 neurotoxic dimeric phospholipase A2, e.g. Mojave toxin (MTX), and less toxic type B venoms, 62 which lack MTX, but are rich in snake venom metalloproteinases (SVMPs) with haemorrhagic 63 activity [10]. Both types seem randomly distributed across the phylogeny of rattlesnakes, and 64 sometimes co-occur within populations of a single species. The Mohave rattlesnake, Crotalus 65 scutulatus, is well-known for displaying both venom strategies across a continuous distributional 66 range in the North American deserts ( Figure 1A) [11][12][13]. This species thus represents an ideal 67 system to investigate the...

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Phenotypic Variation in Mojave Rattlesnake (Crotalus scutulatus) Venom Is Driven by Four Toxin Families

Cited by 34 publications

References 61 publications

Trait differentiation and modular toxin expression in palm-pitvipers

Trait differentiation and modular toxin expression in palm-pitvipers

Many options, few solutions: over 60 million years snakes converged on a few optimal venom formulations

When one phenotype is not enough – divergent evolutionary trajectories govern venom variation in a widespread rattlesnake species

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