Biology subjects

Denton, R.

Publications and source records attributed to Denton, R..

4 recordsLinked to original sources

bioRxiv2026

Kinetic Lipidomics: Quantifying in vivo changes in lipid metabolism using metabolic labeling

Lipid metabolism reflects the dynamic balance between metabolic turnover and concentration. Kinetic mass spectrometry (MS) enables direct quantification of molecular turnover in vivo. Previous work has shown that MS-based kinetic proteomics has provided powerful insights into proteome regulation. Analogous lipidome-wide kinetic measurements remain limited by challenges in defining molecule-specific labeling behavior. Here, we extend kinetic MS to untargeted lipidomics. Isotope labeling with deuterated water (2H2O) is commonly used for monitoring turnover of palmitate and other select lipids by measuring labeling of stable C-H positions with deuterium (2H). Here, we extend the deuterium-incorporation model underlying these targeted lipid turnover assays to support untargeted analysis of all detectable lipids. This allows us to empirically quantify the effective fraction of endogenous synthesis (Asyn) and the turnover rate (k) across hundreds of lipid species simultaneously. One central barrier to lipidome-wide kinetic modeling is determining the endogenous number of deuterium-labeling sites for each molecule (nL) which is required to estimate Asyn and k accurately. The nL value is an essential component of biological kinetic assays. In kinetic proteomics, curated amino acid nL libraries enable peptide-level modeling by summing sequence-specific labeling-site values, but comparable resources are lacking for lipids and may not generalize across metabolic states or non-mammalian systems. Yet, gaps remain for lipids and for amino acids in modified metabolic conditions or non-mammalian biologies. Here, we empirically determine lipid nL values and validate the process with peptides against an nL library. To evaluate this strategy in a biologically relevant setting, we applied it to brain tissue from transgenic mice expressing human ApoE isoforms, where altered lipid transport and metabolism are implicated in Alzheimers disease risk. These data validate the method in a clinically relevant context and suggest that genotype-dependent metabolism can alter empirically determined lipid nL values.

biochemistry↗

bioRxiv2024

Genome composition predicts physiological response to environmental change in polyploid salamanders

Multi-trait analyses can be used to measure the differential performance of phenotypic traits in species complexes. Hybridization within these complexes can result in a mismatch between mitochondrial and nuclear DNA that may lead to reduced performance and acclimation capacity in hybrids. To test the effect of this mismatch on physiology, we compared physiological performance and acclimation capacity of metabolic rate (VCO2) and total resistance to water loss (rT) between two sexual Ambystoma species and a closely related unisexual lineage. We also separated unisexuals by their unique biotypes to determine how physiology varies with subgenomic composition. We found that unisexual biotypes exhibited phenotypes more like their related sexual species than to other unisexuals. We also found a trade-off between rT and VCO2, with increasing rT resulting in a decrease in VCO2. Although we did not find evidence for mitonuclear mismatch, our results indicate that genomic composition of hybrids may be a suitable predictor of hybrid trait performance. Multi-trait analyses are imperative for understanding variation in phenotypic diversity, providing insight into how this diversity affects species responses to environmental change.

physiology↗

bioRxiv2023

A Conceptual Framework for Host-Associated Microbiomes of Hybrid Organisms

Hybridization between organisms from evolutionarily distinct lineages can have profound consequences on organism ecology, with cascading effects on fitness and evolution. Most studies of hybrid organisms have focused on organismal traits, for example various aspects of morphology and physiology. However, with the recent emergence of holobiont theory, there has been growing interest in understanding how hybridization impacts and is impacted by host-associated microbiomes. Better understanding of the interplay between host hybridization and host-associated microbiomes has the potential to provide insight into both the roles of host-associated microbiomes as dictators of host performance as well as the fundamental rules governing host-associated microbiome assembly. Unfortunately, there is a current lack of frameworks for understanding the structure of host-associated microbiomes of hybrid organisms. In this paper, we develop four conceptual models describing possible relationships between the host-associated microbiomes of hybrids and their progenitor or parent taxa. We then integrate these models into a quantitative 4H index and present a new R package for calculation, visualization, and analysis of this index. Finally, we demonstrate how the 4H index can be used to compare hybrid microbiomes across disparate plant and animal systems.

ecology↗

bioRxiv2018

Genome-specific histories of divergence and introgression between an allopolyploid unisexual salamander lineage and two sexual species

Quantifying genetic introgression between sexual species and polyploid lineages traditionally thought to be asexual is an important step in understanding what factors drive the longevity of putatively asexual groups. However, the presence of multiple distinct subgenomes within a single lineage provides a significant logistical challenge to evaluating the origin of genetic variation in most polyploids. Here, we capitalize on three recent innovations--variation generated from ultraconserved elements (UCEs), bioinformatic techniques for assessing variation in polyploids, and model-based methods for evaluating historical gene flow--to measure the extent and tempo of introgression over the evolutionary history of an allopolyploid lineage of all-female salamanders and two ancestral sexual species. We first analyzed variation from more than a thousand UCEs using a reference mapping method developed for polyploids to infer subgenome specific patterns of variation in the all-female lineage. We then used PHRAPL to choose between sets of historical models that reflected different patterns of introgression and divergence between the genomes of the parental species and the same genomes found within the polyploids. Our analyses support a scenario in which the genomes sampled in unisexuals salamanders were present in the lineage [~]3.4 million years ago, followed by an extended period of divergence from their parental species. Recent secondary introgression has occurred at different times between each sexual species and their representative genomes within the unisexuals during the last 500,000 years. Sustained introgression of sexual genomes into the unisexual lineage has been the defining characteristic of their reproductive mode, but this study provides the first evidence that unisexual genomes have also undergone long periods of divergence without introgression. Unlike other unisexual, sperm-dependent taxa in which introgression is rare, the alternating periods of divergence and introgression between unisexual salamanders and their sexual relatives could reveal the scenarios in which the influx of novel genomic material is favored and potentially explain why these salamanders are among the oldest described unisexual animals.

evolutionary biology↗