Biology subjects

Karchner, S. I.

Publications and source records attributed to Karchner, S. I..

3 recordsLinked to original sources

bioRxiv2024

Environmental and Population influences on Mummichog (Fundulus heteroclitus) Gut Microbiomes

The mummichog, Fundulus heteroclitus, an abundant estuarine fish broadly distributed along the eastern coast of North America, has repeatedly evolved tolerance to otherwise lethal levels of aromatic hydrocarbon exposure. This tolerance is linked to reduced activation of the aryl hydrocarbon receptor (AHR) signaling pathway. In other animals, the AHR has been shown to influence the gastrointestinal-associated microbial community, or gut microbiome, particularly when activated by the model toxic pollutant 3,3,4,4,5-pentachlorobiphenyl (PCB-126) and other dioxin-like compounds. In order to understand host population and PCB-126 exposure effects on mummichog gut microbiota, we sampled two populations of wild fish, one from a PCB-contaminated environment (New Bedford Harbor, MA) and the other from a non-polluted location (Scorton Creek, MA), as well as laboratory-reared F2 generation fish originating from each of these populations. We examined the bacteria and archaea associated with the gut of these fish using amplicon sequencing of small subunit ribosomal RNA genes. Fish living in the PCB-polluted site had high microbial alpha and beta diversity and an altered microbial network structure compared to fish from the non-polluted site. These differences between wild fish were not present in laboratory-reared F2 fish that originated from the same populations. Microbial compositional differences existed between the wild and lab-reared fish, with the wild fish dominated by Vibrionaceae and the lab-reared fish by Enterococceae. These results suggest that mummichog habitat and/or environmental conditions has a stronger influence on the mummichog gut microbiome compared to population or hereditary-based influences. Mummichog are important eco-evolutionary model organisms; this work reveals their importance for exploring host-environmental-microbiome dynamics.

ecology↗

bioRxiv2023

Independently evolved pollution resistance in four killifish populations is largely explained by few variants of large effect

The genetic architecture of phenotypic traits can affect the mode and tempo of trait evolution. Human-altered environments can impose strong natural selection, where successful evolutionary adaptation requires swift and large phenotypic shifts. In these scenarios, theory predicts the influence of few adaptive variants of large effect, but empirical studies that have revealed the genetic architecture of rapidly evolved phenotypes are rare, especially for populations inhabiting polluted environments. Fundulus killifish have repeatedly evolved adaptive resistance to extreme pollution in urban estuaries. Prior studies, including genome scans for signatures of natural selection, have revealed some of the genes and pathways important for evolved pollution resistance, and provide context for the genotype-phenotype association studies reported here. We created multiple quantitative trait locus (QTL) mapping families using progenitors from four different resistant populations, and genetically mapped variation in sensitivity (developmental perturbations) following embryonic exposure to a model toxicant PCB-126. We found that a few large-effect QTL loci accounted for resistance to PCB- mediated developmental toxicity. QTLs harbored candidate genes that govern the regulation of aryl hydrocarbon receptor (AHR) signaling, where some (but not all) of these QTL loci were shared across all populations, and some (but not all) of these loci showed signatures of recent natural selection in the corresponding wild population. Some strong candidate genes for PCB resistance inferred from genome scans in wild populations were identified as QTL, but some key candidate genes were not. We conclude that rapidly evolved resistance to the developmental defects normally caused by PCB-126 is governed by few genes of large effect. However, other aspects of resistance beyond developmental phenotypes may be governed by additional loci, such that comprehensive resistance to PCB-126, and to the mixtures of chemicals that distinguish urban estuaries more broadly, may be more genetically complex.

evolutionary biology↗

bioRxiv2020

PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

Chemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3 UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g., ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

pharmacology and toxicology↗