Biology subjects

Clark, B. W.

Publications and source records attributed to Clark, B. W..

3 recordsLinked to original sources

bioRxiv2025

Early-life PBDE flame retardant exposures cause neurobehavioral alterations in fish that persist into adulthood and vary by sex and route of exposure

Developing organisms exhibit varying susceptibility to environmental pollutants depending on the timing of exposure during development. Early-life development is particularly vulnerable, and many marine species spend early life in nearshore environments, elevating their risk of pollutant exposure. Polybrominated diphenyl ether (PBDE) flame retardants are persistent and ubiquitous pollutants, particularly in nearshore marine environments. They disrupt early-life development and pose ongoing risks for ocean health. However, whether early-life exposure influences neurotoxic effects, and whether those effects are durable throughout life, remains poorly understood. Using Fundulus heteroclitus, we tested whether early-life exposure to 2,2,4,4,5-pentaBDE (BDE-99) leads to persistent behavioral and molecular alterations in adulthood and whether outcomes differ by exposure route. We conducted two complementary experiments comparing progenitor (maternal) exposure and direct waterborne exposure during embryonic development. Similar doses to developing fish were achieved in both experiments. After hatch, all fish were reared in clean water until adulthood over two years later, at which time we assessed impacts on behavior and brain gene expression. Both exposure routes led to long-term hyperactivity and reduced anxiety-like behavior, but specific effects varied by dose and sex. Progenitor exposure altered behavior and the brain transcriptome in F1 males (females not tested), whereas direct embryonic exposure affected behavior in females and not males. These findings highlight the importance of maternal influences, such as chemical metabolites, altered lipid provisioning, small molecules, and epigenetic imprinting, alongside chemical transfer, in shaping the long-term persistence of behavioral and molecular effects from early-life exposure. The distinct effects between exposure routes suggest that dosing with chemical alone is not the only determinant of toxicity. We conclude that maternal factors that are modified by exposure significantly contribute to health outcomes in developing offspring, emphasizing the need to consider exposure route when assessing risks from persistent pollutants. Given that maternal and environmental exposures co-occur in nature, future studies should assess their combined impacts to better predict real-world risks.

pharmacology and toxicology↗

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↗