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1. Venom Gene Sequence Diversity and Expression Jointly Shape Diet Adaptation in Pitvipers

   https://doi.org/10.1093/molbev/msac082  

   Mason, Andrew J.; Holding, Matthew L.; Rautsaw, Rhett M.; Rokyta, Darin R.; Parkinson, Christopher L.; Gibbs, H. Lisle (April 2022, Molecular Biology and Evolution)

   Yoder, Anne (Ed.)

   Abstract Understanding the joint roles of protein sequence variation and differential expression during adaptive evolution is a fundamental, yet largely unrealized goal of evolutionary biology. Here, we use phylogenetic path analysis to analyze a comprehensive venom-gland transcriptome dataset spanning three genera of pitvipers to identify the functional genetic basis of a key adaptation (venom complexity) linked to diet breadth (DB). The analysis of gene-family-specific patterns reveals that, for genes encoding two of the most important venom proteins (snake venom metalloproteases and snake venom serine proteases), there are direct, positive relationships between sequence diversity (SD), expression diversity (ED), and increased DB. Further analysis of gene-family diversification for these proteins showed no constraint on how individual lineages achieved toxin gene SD in terms of the patterns of paralog diversification. In contrast, another major venom protein family (PLA2s) showed no relationship between venom molecular diversity and DB. Additional analyses suggest that other molecular mechanisms—such as higher absolute levels of expression—are responsible for diet adaptation involving these venom proteins. Broadly, our findings argue that functional diversity generated through sequence and expression variations jointly determine adaptation in the key components of pitviper venoms, which mediate complex molecular interactions between the snakes and their prey. 

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2. Effects of pejus and pessimum zone salinity stress on gill proteome networks and energy homeostasis in Oreochromis mossambicus

   https://doi.org/10.1002/pmic.202300121  

   Root, Larken; Kültz, Dietmar (July 2023, PROTEOMICS)

   Abstract Salinity tolerance in fish involves a suite of physiological changes, but a cohesive theory leading to a mechanistic understanding at the organismal level is lacking. To examine the potential of adapting energy homeostasis theory in the context of salinity stress in teleost fish,Oreochromis mossambicuswere acclimated to hypersalinity at multiple rates and durations to determine salinity ranges of tolerance and resistance. Over 3000 proteins were quantified simultaneously to analyze molecular phenotypes associated with hypersalinity. A species‐ and tissue‐specific data‐independent acquisition (DIA) assay library of MSMS spectra was created. Protein networks representing complex molecular phenotypes associated with salinity acclimation were generated.O. mossambicushas a wide “zone of resistance” from 75 g/kg salinity to 120 g/kg. Crossing into the zone of resistance resulted in marked phenotypic changes including blood osmolality over 400 mOsm/kg, reduced body condition, and cessation of feeding. Protein networks impacted by hypersalinity consist of electron transport chain (ETC) proteins and specific osmoregulatory proteins. Cytoskeletal, cell adhesion, and extracellular matrix proteins are enriched in networks that are sensitive to the critical salinity threshold. These network analyses identify specific proteome changes that are associated with distinct zones described by energy homeostasis theory and distinguish them from general hypersalinity‐induced proteome changes. 

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3. Molecular mechanisms underlying intraspecific variation in snake venom

   Amazonas, DR (January 2018, Journal of proteomics)

   Understanding the molecular mechanisms that underlie snake venom variability provides important clues for understanding how the biological functions of this powerful toxic arsenal evolve. Here we analyzed in detail individual transcripts and venom protein isoforms produced by five specimens of a venomous snake (Bothrops atrox) from two nearby but genetically distinct populations from the Brazilian Amazon rainforest showing functional similarities in venom properties. Individual variation was observed among the venoms of these specimens, but the overall abundance of each general toxin family was conserved both in transcripts and in venom protein levels. However, when expression of independent paralogues was analyzed, remarkable differences were observed within and among each toxin group both between individuals and between populations. Transcripts for functionally essential venom proteins (“housekeeping” proteins) are highly expressed in all specimens and show similar transcription/translation rates. In contrast, other paralogues show lower expression levels and the toxins they code for vary among different individuals. These results provide support for the idea that that expression and translational differences play a greater role in defining adaptive variation in venom phenotypes than does sequence variation in protein coding genes and that convergent adaptive venom phenotypes can be generated through different molecular mechanisms. 

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

   https://doi.org/10.1101/gr.276251.121  

   Perry, Blair W.; Gopalan, Siddharth S.; Pasquesi, Giulia I.M.; Schield, Drew R.; Westfall, Aundrea K.; Smith, Cara F.; Koludarov, Ivan; Chippindale, Paul T.; Pellegrino, Mark W.; Chuong, Edward B.; et al (June 2022, Genome Research)

   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 cis -regulatory sequences (enhancers and promoters), trans -regulatory transcription factors, and integrated signaling cascades involved in the regulation of snake venom genes. We find evidence that two conserved vertebrate pathways, the extracellular signal-regulated kinase and unfolded protein response pathways, were co-opted to regulate snake venom. In one large venom gene family (snake venom serine proteases), this co-option was likely facilitated by the activity of transposable elements. Patterns of snake venom gene enhancer conservation, in some cases spanning 50 million yr of lineage divergence, highlight early origins and subsequent lineage-specific adaptations that have accompanied the evolution of venom regulatory architecture. We also identify features of chromatin structure involved in venom regulation, including topologically associated domains and CTCF loops that underscore the potential importance of novel chromatin structure to coevolve when duplicated genes evolve new regulatory control. Our findings provide a model for understanding how novel regulatory systems may evolve through a combination of genomic processes, including tandem duplication of genes and regulatory sequences, cis -regulatory sequence seeding by transposable elements, and diverse transcriptional regulatory proteins controlled by a co-opted regulatory cascade. 

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5. Ontogenetic Change in the Venom of Mexican Black-Tailed Rattlesnakes (Crotalus molossus nigrescens)

   https://doi.org/10.3390/toxins10120501  

   Borja, Miguel; Neri-Castro, Edgar; Pérez-Morales, Rebeca; Strickland, Jason; Ponce-López, Roberto; Parkinson, Christopher; Espinosa-Fematt, Jorge; Sáenz-Mata, Jorge; Flores-Martínez, Esau; Alagón, Alejandro; et al (December 2018, Toxins)

   null (Ed.)

   Ontogenetic changes in venom composition have important ecological implications due the relevance of venom in prey acquisition and defense. Additionally, intraspecific venom variation has direct medical consequences for the treatment of snakebite. However, ontogenetic changes are not well documented in most species. The Mexican Black-tailed Rattlesnake (Crotalus molossus nigrescens) is large-bodied and broadly distributed in Mexico. To document venom variation and test for ontogenetic changes in venom composition, we obtained venom samples from twenty-seven C. m. nigrescens with different total body lengths (TBL) from eight states in Mexico. The primary components in the venom were detected by reverse-phase HPLC, western blot, and mass spectrometry. In addition, we evaluated the biochemical (proteolytic, coagulant and fibrinogenolytic activities) and biological (LD50 and hemorrhagic activity) activities of the venoms. Finally, we tested for recognition and neutralization of Mexican antivenoms against venoms of juvenile and adult snakes. We detected clear ontogenetic venom variation in C. m. nigrescens. Venoms from younger snakes contained more crotamine-like myotoxins and snake venom serine proteinases than venoms from older snakes; however, an increase of snake venom metalloproteinases was detected in venoms of larger snakes. Venoms from juvenile snakes were, in general, more toxic and procoagulant than venoms from adults; however, adult venoms were more proteolytic. Most of the venoms analyzed were hemorrhagic. Importantly, Mexican antivenoms had difficulties recognizing low molecular mass proteins (<12 kDa) of venoms from both juvenile and adult snakes. The antivenoms did not neutralize the crotamine effect caused by the venom of juveniles. Thus, we suggest that Mexican antivenoms would have difficulty neutralizing some human envenomations and, therefore, it may be necessary improve the immunization mixture in Mexican antivenoms to account for low molecular mass proteins, like myotoxins. 

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