Biology subjects

Jackson, C. E.

Publications and source records attributed to Jackson, C. E..

4 recordsLinked to original sources

bioRxiv2026

Role of Nutritional Status on Arsenic Toxicity in Daphnia pulex: A Transcriptomic Perspective on Individual and Interactive Effects

Inorganic arsenic is a widespread environmental contaminant and known human carcinogen, yet the mechanisms by which nutritional status modulates arsenic toxicity remain poorly understood. Here, we investigated the main and interactive effects of environmentally relevant concentrations of arsenic, low food quantity, and low dietary phosphorus supply on genome-wide gene expression in aquatic grazer Daphnia pulex. Differential gene expression analysis identified a total of 1,213 differently expressed genes with interactions of arsenic x nutrient stressors accounting for approximately 70% of the transcriptomic response. Low phosphorus emerged as a dominant main effect stressor and it also had a profound impact on transcription as a co-stressor. The low phosphorus x arsenic interaction exhibited the greatest transcriptional impact (435 DE genes), revealing that phosphorus limitation rather than food quantity influences arsenic toxicity at the gene expression level. Gene ontology and Pathway Activation Analysis revealed that main effects elicited simple yet distinct functional responses, whereas arsenic x nutrient interactions induced complex pathway-level disruptions including cell signaling, detoxification metabolism, DNA repair mechanisms, and energy homeostasis. Further assessment of gene expression revealed that all arsenic x nutrient interactions are antagonistic supporting previous literature that found arsenic behaves antagonistically as a co-stressor. Our results provide mechanistic insight into how nutritional status modulates arsenic toxicity and highlights the importance of considering arsenic x nutrient co-stressor interactions.

pharmacology and toxicology↗

bioRxiv2025

Discovery and evaluation of cadmium-adapted Daphnia pulex genotypes in a region of historical mining reveals adaptation protects the germline from cadmium-induced mutations

Exposure to chemical pollutants can alter the rate, and genome-wide distribution of germline mutations. However, studies measuring the effect of chemical exposure on mutation rate and spectra have not considered the ecological and evolutionary backgrounds of studied genotypes, which could influence the rates and patterns of germline mutations in altered environments, e.g., chemical pollution. Utilizing a study of natural Daphnia pulex populations, we conducted a comprehensive experiment to test our hypothesis that adaptation to chemical pollution also protects the germline from mutagenesis. We, 1) identified Daphnia pulex populations that have adapted to live in mining-devastated regions by increasing their cadmium tolerance. 2) We completed a mutation-accumulation (MA) experiment with an adapted genotype to measure the germline mutation rate in both control conditions and an environmentally relevant cadmium concentration. 3) We compared these MA experiment results to a previously reported, identically designed MA experiment with a nonadapted genotype. We report that patterns of cadmium-induced mutagenesis in the adapted genotype were reversed compared to our previous observations in the nonadapted genotype. Cadmium exposure altered the single nucleotide mutation (SNM) rate in the same genome regions in adapted and nonadapted genotypes, but the rates were changed in opposite directions. Cadmium also altered specific SNM classes in these genotypes in opposite directions. The reversal of mutational trends in the adapted genotype suggests protection against cadmium genotoxicity. We further demonstrate that adapted populations have elevated gene copy-number and expression levels of metallothionein, the protein that protects against cadmium toxicity by binding to cadmium irreversibly.

evolutionary biology↗

bioRxiv2023

Enzalutamide Induces Cytotoxicity in Desmoplastic Small Round Cell Tumor Independent of the Androgen Receptor

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare, pediatric cancer caused by the EWSR1::WT1 fusion protein. DSRCT predominantly occurs in males, which comprise 80-90% of the patient population. While the reason for this male predominance remains unknown, one hypothesis is that the androgen receptor (AR) plays a critical role in DSRCT and elevated testosterone levels in males help drive tumor growth. Here, we demonstrate that AR is highly expressed in DSRCT relative to other fusion-driven sarcomas and that the AR antagonists enzalutamide and flutamide reduce DSRCT growth. However, despite these findings, which suggest an important role for AR in DSRCT, we show that DSRCT cell lines form xenografts in female mice at the same rate as male mice and AR depletion does not significantly alter DSRCT growth in vitro. Further, we find that AR antagonists reduce DSRCT growth in cells depleted of AR, establishing an AR-independent mechanism of action. These findings suggest that AR dependence is not the reason for male predominance in DSRCT and that AR-targeted therapies may provide therapeutic benefit primarily through an AR-independent mechanism that requires further elucidation.

cancer biology↗

bioRxiv2021

Chromosomal rearrangements preserve adaptive divergence in ecological speciation

Despite increasing empirical evidence that chromosomal rearrangements may play an important role in adaptive divergence and speciation, the degree to which divergent genomic regions are associated with chromosomal rearrangements remains unclear. In this study, we provide the first whole-genome analyses of ecological speciation and chromosomal evolution in a Daphnia species complex, using chromosome-scale assemblies and natural-population sequencing of the recently diverged species pair, Daphnia pulicaria and Daphnia pulex, which occupy distinct yet overlapping habitats in North America, and the outgroup species Daphnia obtusa. Our results describe a mixed mode of geographic divergence (isolation with secondary contact) resulting in a heterogeneous landscape of genomic divergence. Large contiguous "continents of divergence" encompass over one third of the genome (36%) and contain nearly all the fixed differences (94%) between the species, while the background genome has been homogenized. Chromosomal rearrangements between species, including inversions and intrachromosomal translocations, are associated with the continents of divergence and capture multiple adaptive alleles in genes and pathways thought to contribute to the species phenotypic differences.

evolutionary biology↗