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  1. Abstract Background

    Snakes exhibit extreme intestinal regeneration following months-long fasts that involves unparalleled increases in metabolism, function, and tissue growth, but the specific molecular control of this process is unknown. Understanding the mechanisms that coordinate these regenerative phenotypes provides valuable opportunities to understand critical pathways that may control vertebrate regeneration and novel perspectives on vertebrate regenerative capacities.


    Here, we integrate a comprehensive set of phenotypic, transcriptomic, proteomic, and phosphoproteomic data from boa constrictors to identify the mechanisms that orchestrate shifts in metabolism, nutrient uptake, and cellular stress to direct phases of the regenerative response. We identify specific temporal patterns of metabolic, stress response, and growth pathway activation that direct regeneration and provide evidence for multiple key central regulatory molecules kinases that integrate these signals, including major conserved pathways like mTOR signaling and the unfolded protein response.


    Collectively, our results identify a novel switch-like role of stress responses in intestinal regeneration that forms a primary regulatory hub facilitating organ regeneration and could point to potential pathways to understand regenerative capacity in vertebrates.

  2. Abstract

    The study of recently diverged lineages whose geographical ranges come into contact can provide insight into the early stages of speciation and the potential roles of reproductive isolation in generating and maintaining species. Such insight can also be important for understanding the strategies and challenges for delimiting species within recently diverged species complexes. Here, we use mitochondrial and nuclear genetic data to study population structure, gene flow and demographic history across a geographically widespread rattlesnake clade, the western rattlesnake species complex (Crotalus cerberus, Crotalus viridis, Crotalus oreganus and relatives), which contains multiple lineages with ranges that overlap geographically or contact one another. We find evidence that the evolutionary history of this group does not conform to a bifurcating tree model and that pervasive gene flow has broadly influenced patterns of present-day genetic diversity. Our results suggest that lineage diversity has been shaped largely by drift and divergent selection in isolation, followed by secondary contact, in which reproductive isolating mechanisms appear weak and insufficient to prevent introgression, even between anciently diverged lineages. The complexity of divergence and secondary contact with gene flow among lineages also provides new context for why delimiting species within this complex has been difficult and contentiousmore »historically.

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  3. ABSTRACT The venom glands of reptiles, particularly those of front-fanged advanced snakes, must satisfy conflicting biological demands: rapid synthesis of potentially labile and highly toxic proteins, storage in the gland lumen for long periods, stabilization of the stored secretions, immediate activation of toxins upon deployment and protection of the animal from the toxic effects of its own venom. This dynamic system could serve as a model for the study of a variety of different phenomena involving exocrine gland activation, protein synthesis, stabilization of protein products and secretory mechanisms. However, these studies have been hampered by a lack of a long-term model that can be propagated in the lab (as opposed to whole-animal studies). Numerous attempts have been made to extend the lifetime of venom gland secretory cells, but only recently has an organoid model been shown to have the requisite qualities of recapitulation of the native system, self-propagation and long-term viability (>1 year). A tractable model is now available for myriad cell- and molecular-level studies of venom glands, protein synthesis and secretion. However, venom glands of reptiles are not identical, and many differ very extensively in overall architecture, microanatomy and protein products produced. This Review summarizes the similarities among and differencesmore »between venom glands of helodermatid lizards and of rear-fanged and front-fanged snakes, highlighting those areas that are well understood and identifying areas where future studies can fill in significant gaps in knowledge of these ancient, yet fascinating systems.« less
    Free, publicly-accessible full text available April 1, 2023
  4. Abstract Male-biased mutation rates occur in a diverse array of organisms. The ratio of male-to-female mutation rate may have major ramifications for evolution across the genome, and for sex-linked genes in particular. In ZW species, the Z chromosome is carried by males two-thirds of the time, leading to the prediction that male-biased mutation rates will have a disproportionate effect on the evolution of Z-linked genes relative to autosomes and the W chromosome. Colubroid snakes (including colubrids, elapids, and viperids) have ZW sex determination, yet male-biased mutation rates have not been well studied in this group. Here we analyze a population genomic dataset from rattlesnakes to quantify genetic variation within and genetic divergence between species. We use a new method for unbiased estimation of population genetic summary statistics to compare variation between the Z chromosome and autosomes and to calculate net nucleotide differentiation between species. We find evidence for a 2.03-fold greater mutation rate in male rattlesnakes relative to females, corresponding to an average μZ/μA ratio of 1.1. Our results from snakes are quantitatively similar to birds, suggesting that male-biased mutation rates may be a common feature across vertebrate lineages with ZW sex determination.
  5. Ponty, Yann (Ed.)
    Abstract Summary Here, we present PhyloWGA, an open source R package for conducting phylogenetic analysis and investigation of whole genome data. Availabilityand implementation Available at Github ( Supplementary information Supplementary data are available at Bioinformatics online.
  6. Abstract Despite the extensive body of research on snake venom, many facets of snake venom systems, such as the physiology and regulation of the venom gland itself, remain virtually unstudied. Here, we use time series gene expression analyses of the rattlesnake venom gland in comparison with several non-venom tissues to characterize physiological and cellular processes associated with venom production and to highlight key distinctions of venom gland cellular and physiological function. We find consistent evidence for activation of stress response pathways in the venom gland, suggesting that mitigation of cellular stress is a crucial component of venom production. Additionally, we demonstrate evidence for an unappreciated degree of cellular and secretory activity in the steady state venom gland relative to other secretory tissues and identify vacuolar ATPases as the likely mechanisms driving acidification of the venom gland lumen during venom production and storage.
  7. Arkhipova, Irina (Ed.)
    Abstract Microchromosomes are common yet poorly understood components of many vertebrate genomes. Recent studies have revealed that microchromosomes contain a high density of genes and possess other distinct characteristics compared with macrochromosomes. Whether distinctive characteristics of microchromosomes extend to features of genome structure and organization, however, remains an open question. Here, we analyze Hi-C sequencing data from multiple vertebrate lineages and show that microchromosomes exhibit consistently high degrees of interchromosomal interaction (particularly with other microchromosomes), appear to be colocalized to a common central nuclear territory, and are comprised of a higher proportion of open chromatin than macrochromosomes. These findings highlight an unappreciated level of diversity in vertebrate genome structure and function, and raise important questions regarding the evolutionary origins and ramifications of microchromosomes and the genes that they house.
  8. Geometric morphometrics (GM) is a powerful analytical approach for evaluating phenotypic variation relevant to taxonomy and systematics, and as with any statistical methodology, requires adherence to fundamental assumptions for inferences to be strictly valid. An important consideration for GM is how landmark configurations, which represent sets of anatomical loci for evaluating shape variation through Cartesian coordinates, relate to underlying homology (Zelditch et al. 1995; Polly 2008). Perhaps more so than with traditional morphometrics, anatomical homology is a crucial assumption for GM because of the mathematical and biological interpretations associated with shape change depicted by deformation grids, such as the thin plate spline (Klingenberg 2008; Zelditch et al. 2012). GM approaches are often used to analyze shapes or outlines of structures, which are not necessarily related to common ancestry, and in this respect GM approaches that use linear semi-landmarks and related methods are particularly amenable to evaluating primary homology, or raw similarity between structures (De Pinna 1991; Palci & Lee 2019). This relaxed interpretation of homology that focuses more on recognizable and repeatable landmarks is defensible so long as authors are clear regarding the purpose of the analyses and in defining their landmark configurations (Palci & Lee 2019). Secondary homology, ormore »similarity due to common ancestry, can also be represented with GM methods and is often assumed to be reflected in fixed Type 1 (juxtaposition of tissues) or Type 2 (self-evident geometry) landmarks (Bookstein 1991).« less
  9. Leitner, Thomas (Ed.)
    Abstract Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia’s inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited.