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Richard T. Di Giulio - One of the best experts on this subject based on the ideXlab platform.
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hepatic responses of juvenile Fundulus heteroclitus from pollution adapted and nonadapted populations exposed to elizabeth river sediment extract
Toxicologic Pathology, 2016Co-Authors: Amanda K Riley, Daniel R Brown, Melissa Chernick, David E Hinton, Richard T. Di GiulioAbstract:Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries region of the Elizabeth River, Virginia, have passed polycyclic aromatic hydrocarbon (PAH) resistance to their offspring as evidenced by early life stage testing of developmental toxicity after exposure to specific PAHs. Our study focused on environmentally relevant PAH mixtures in the form of Elizabeth River sediment extract (ERSE). Juvenile (5 month) F1 progeny of pollution-adapted Atlantic Wood (AW) parents and of reference site (King's Creek [KC]) parents were exposed as embryos to ERSE. Liver alterations, including nonneoplastic lesions and microvesicular vacuolation, were observed in both populations. ERSE-exposed KC fish developed significantly more alterations than unexposed KC fish. Interestingly, unexposed AW killifish developed significantly more alterations than unexposed KC individuals, suggesting that AW juveniles are not fully protected from liver disease; rapid growth of juvenile fish may also be an accelerating factor for tumorigenesis. Because recent reports show hepatic tumor formation in adult AW fish, the differing responses from the 2 populations provided a way to determine whether embryo toxicity protection extends to juveniles. Future investigations will analyze older life stages of killifish to determine differences in responses related to chronic disease.
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compound and mixture specific differences in resistance to polycyclic aromatic hydrocarbons and pcb 126 among Fundulus heteroclitus subpopulations throughout the elizabeth river estuary virginia usa
Environmental Science & Technology, 2013Co-Authors: Bryan W. Clark, Heather M Stapleton, Ellen M Cooper, Richard T. Di GiulioAbstract:Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries Superfund Site (Elizabeth River, Portsmouth, VA, USA) are resistant to the acute toxicity and cardiac teratogenesis caused by high levels of polycyclic aromatic hydrocarbons (PAHs) from creosote. The resistance is linked to down regulation of the aryl hydrocarbon receptor (AHR) pathway. We investigated the association between CYP1 activity, as a marker of potential AHR pathway suppression, and contaminant resistance in killifish subpopulations from sites throughout the estuary that varied significantly in PAH contamination level. Adult killifish and sediments were collected from seven sites across approximately 13.7 km in river length within the estuary and from a nearby reference site. Sediment PAH levels were determined using gas chromatography mass spectrometry. Embryos obtained via manual spawning were exposed to individual AHR agonists and PAH mixtures 24 h post fertilization (hpf); CYP1 activity was determined by in o...
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Fundulus heteroclitus adapted to PAHs are cross-resistant to multiple insecticides
Ecotoxicology, 2012Co-Authors: Bryan W. Clark, Richard T. Di GiulioAbstract:Atlantic killifish ( Fundulus heteroclitus ) from the Atlantic Wood Superfund site on the Elizabeth River (ER), VA are dramatically resistant to the acute toxicity and teratogenesis caused by polycyclic aromatic hydrocarbons (PAHs). To understand the consequences of adaptation to chronic PAH pollution, we have attempted to further define the chemical tolerance associated with this resistance. An important component of the PAH adaptation of ER fish is the dramatic down-regulation of the aryl hydrocarbon receptor (AHR) pathway, resulting in decreased cytochrome p450 (CYP) 1 activity. Herein, we compared the susceptibility to several insecticides of ER fish to that of reference site (King's Creek; KC) fish; use of these chemicals as probes of the resistance will help to demonstrate if the contaminant adaptation exhibited by ER fish is broad or narrow and AHR-focused. We hypothesized that ER fish would be less susceptible to the organophosphate chlorpyrifos (activated by CYP) and more susceptible to the pyrethroid permethrin (detoxified by CYP). Comparison of acute toxicity in 5-day-old larvae supported this hypothesis for chlorpyrifos. As expected, chemical up-regulation of CYP by co-exposure to β-naphthoflavone (BNF) enhanced the susceptibility of KC but it did not affect ER larvae. Unexpectedly, ER larvae were much less susceptible to permethrin than KC larvae. However, co-exposure to BNF greatly decreased the susceptibility of KC larvae, indicating that metabolism of permethrin by CYP was protective. Additionally, fish from each population were compared for susceptibility to the carbamate carbaryl, an acute neurotoxicant and weak AHR agonist that induces teratogenesis similar to that caused by PAHs. ER embryos and larvae were less susceptible than KC fish. These results suggest that the adaptive phenotype of ER fish is multi-faceted and that aspects other than CYP response are likely to greatly affect their response to contaminants.
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genotoxicity in atlantic killifish Fundulus heteroclitus from a pah contaminated superfund site on the elizabeth river virginia
Ecotoxicology, 2011Co-Authors: Dawoon Jung, Cole W. Matson, Leonard B Collins, Geoff Laban, Heather M Stapleton, John W Bickham, James A Swenberg, Richard T. Di GiulioAbstract:The Atlantic Wood Industries Superfund site (AWI) on the Elizabeth River in Portsmouth, VA is heavily contaminated with polycyclic aromatic hydrocarbons (PAHs) from a wood treatment facility. Atlantic killifish, or mummichog (Fundulus heteroclitus), at this Superfund site are exposed to very high concentrations of several carcinogens. In this study, we measured PAH concentrations in both fish tissues and sediments. Concurrently, we assessed different aspects of genotoxicity in the killifish exposed in situ. Both sediment and tissue PAH levels were significantly higher in AWI samples, relative to a reference site, but the chemistry profile was different between sediments and tissues. Killifish at AWI exhibited higher levels of DNA damage compared to reference fish, as measured via the flow cytometric method (FCM), and the damage was consistent with sediment PAH concentrations. Covalent binding of benzo[a]pyrene (BaP) metabolites to DNA, as measured via LC–MS/MS adduct detection methods, were also elevated and could be partially responsible for the DNA damage. Using similar LC–MS/MS methods, we found no evidence that oxidative DNA adducts had a role in observed genotoxicity.
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ahr2 mediates cardiac teratogenesis of polycyclic aromatic hydrocarbons and pcb 126 in atlantic killifish Fundulus heteroclitus
Aquatic Toxicology, 2010Co-Authors: Bryan W. Clark, Dawoon Jung, Cole W. Matson, Richard T. Di GiulioAbstract:Exposure of developing fish to polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) results in a suite of defects including cardiac malformation, pericardial and yolk sac edema, craniofacial defects, and hemorrhaging. Several populations of Atlantic killifish or mummichog (Fundulus heteroclitus) on the Atlantic coast of the United States are resistant to the developmental and acute toxicity caused by PAHs and HAHs; this has made Fundulus a valuable model for studying aryl hydrocarbon sensitivity and adaptation. In order to further increase the utility of Fundulus, better understanding of the components of the molecular pathways governing aryl hydrocarbon response in Fundulus is required. The aryl hydrocarbon receptor (AHR) is known to mediate many of the toxic responses to PAHs and HAHs. A single AHR has been identified in mammals, but Fundulus has two AHRs and their relative roles are not clear. In the current study, translation-blocking and splice-junction morpholino gene knockdown was used to determine the roles of AHR1 and AHR2 in mediating cardiac teratogenesis induced by β-naphthoflavone (BNF), benzo[k]fluoranthene (BkF), and 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126). Here we report that AHR2 and not AHR1 knockdown resulted in rescue of teratogenicity induced by BNF, BkF, and PCB-126. These data demonstrate that AHR2 is the primary mediator of cardiac teratogenesis caused by multiple aryl hydrocarbons in Fundulus and suggest that suppression of the AHR pathway through modulation of AHR2 is a plausible mechanism for PAH resistance in adapted fish. Additionally, this is the first reported use of splice-junction morpholinos in Fundulus.
Patricia M Schulte - One of the best experts on this subject based on the ideXlab platform.
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evolutionary physiology and genomics in the highly adaptable killifish Fundulus heteroclitus
Comprehensive Physiology, 2020Co-Authors: Douglas L Crawford, Patricia M Schulte, Marjorie F OleksiakAbstract:By investigating evolutionary adaptations that change physiological functions, we can enhance our understanding of how organisms work, the importance of physiological traits, and the genes that influence these traits. This approach of investigating the evolution of physiological adaptation has been used with the teleost fish Fundulus heteroclitus and has produced insights into (i) how protein polymorphisms enhance swimming and development; (ii) the role of equilibrium enzymes in modulating metabolic flux; (iii) how variation in DNA sequences and mRNA expression patterns mitigate changes in temperature, pollution, and salinity; and (iv) the importance of nuclear-mitochondrial genome interactions for energy metabolism. Fundulus heteroclitus provides so many examples of adaptive evolution because their local population sizes are large, they have significant standing genetic variation, and they experience large ranges of environmental conditions that enhance the likelihood that adaptive evolution will occur. Thus, F. heteroclitus research takes advantage of evolutionary changes associated with exposure to diverse environments, both across the North American Atlantic coast and within local habitats, to contrast neutral versus adaptive divergence. Based on evolutionary analyses contrasting neutral and adaptive evolution in F. heteroclitus populations, we conclude that adaptive evolution can occur readily and rapidly, at least in part because it depends on large amounts of standing genetic variation among many genes that can alter physiological traits. These observations of polygenic adaptation enhance our understanding of how evolution and physiological adaptation progresses, thus informing both biological and medical scientists about genotype-phenotype relationships. © 2020 American Physiological Society. Compr Physiol 10:637-671, 2020.
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the effect of acute warming and thermal acclimation on maximum heart rate of the common killifish Fundulus heteroclitus
Journal of Fish Biology, 2019Co-Authors: Hamid Safi, Patricia M Schulte, Yangfan Zhang, Anthony P. FarrellAbstract:Common killifish Fundulus heteroclitus were acclimated to ecologically relevant temperatures (5, 15 and 33°C) and their maximum heart rate (fHmax ) was measured at each acclimation temperature during an acute warming protocol. Acclimation to 33°C increased peak fHmax by up to 32% and allowed the heart to beat rhythmically at a temperature 10°C higher when compared with acclimation to 5°C. Independent of acclimation temperature, peak fHmax occurred about 3°C cooler than the temperature that first produced cardiac arrhythmias. Thus, when compared with previously published values for the critical thermal maximum of F. heteroclitus, the temperature for peak fHmax was cooler and the temperature that first produced cardiac arrhythmias was similar to these critical thermal maxima. The considerable thermal plasticity of fHmax demonstrated in the present study is entirely consistent with eurythermal ecology of killifish, as shown previously for another eurythermal fish Gillichthys mirabilis.
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thermal acclimation and subspecies specific effects on heart and brain mitochondrial performance in a eurythermal teleost Fundulus heteroclitus
The Journal of Experimental Biology, 2017Co-Authors: Dillon J Chung, Heather J Bryant, Patricia M SchulteAbstract:Mitochondrial performance may play a role in setting whole-animal thermal tolerance limits and their plasticity, but the relative roles of adjustments in mitochondrial performance across different highly aerobic tissues remain poorly understood. We compared heart and brain mitochondrial responses to acute thermal challenges and to thermal acclimation using high-resolution respirometry in two locally adapted subspecies of Atlantic killifish (Fundulus heteroclitus). We predicted that 5°C acclimation would result in compensatory increases in mitochondrial performance, while 33°C acclimation would cause suppression of mitochondrial function to minimize the effects of high temperature on mitochondrial metabolism. In contrast, acclimation to both 33 and 5°C decreased mitochondrial performance compared with fish acclimated to 15°C. These adjustments could represent an energetic cost-saving mechanism at temperature extremes. Acclimation responses were similar in both heart and brain; however, this effect was smaller in the heart, which might indicate its importance in maintaining whole-animal thermal performance. Alternatively, larger acclimation effects in the brain might indicate greater thermal sensitivity compared with the heart. We detected only modest differences between subspecies that were dependent on the tissue assayed. These data demonstrate extensive plasticity in mitochondrial performance following thermal acclimation in killifish, and indicate that the extent of these responses differs between tissues, highlighting the importance and complexity of mitochondrial regulation in thermal acclimation in eurytherms.
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Metabolic and regulatory responses involved in cold acclimation in Atlantic killifish, Fundulus heteroclitus
Journal of Comparative Physiology B, 2017Co-Authors: Timothy M Healy, Dillon J Chung, Kyle G. Crowther, Patricia M SchulteAbstract:Ectotherms often respond to prolonged cold exposure by increasing mitochondrial capacity via elevated mitochondrial volume density [ V _V(mit,f)]. In fish, higher V _V(mit,f) is typically associated with increased expression of nuclear respiratory factor 1 (Nrf1), a transcription factor that induces expression of nuclear-encoded respiratory genes. To examine if nrf1 expression or the expression of other genes that regulate mitochondrial biogenesis contribute to changes in whole-organism metabolic rate during cold acclimation, we examined the time course of changes in the expression of these genes and in metabolic rate in Atlantic killifish, Fundulus heteroclitus . Cold acclimation rapidly decreased metabolic rate, but increased the expression of nrf1 more gradually, with a time course that depended on how rapidly the fish were transitioned to low temperature. Cold-induced nrf1 expression was not associated with increases in biochemical indicators of mitochondrial respiratory capacity, suggesting that cold-induced mitochondrial biogenesis may occur without increases in oxidative capacity in this species. These observations imply that changes in nrf1 expression and metabolic rate due to cold acclimation occur through different physiological mechanisms, and that increases in V _V(mit,f) are likely not directly related to changes in metabolic rate with cold acclimation in this species. However, nrf1 expression differed between northern and southern killifish subspecies regardless of acclimation temperature, consistent with observed differences in metabolic rate and V _V(mit,f) at 5 °C between these subspecies. Taken together, these results reveal substantial complexity in the regulation of V _V(mit,f) and mitochondrial capacity with temperature in fish and the relationship of these parameters to metabolic rate.
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warm acclimation improves hypoxia tolerance in Fundulus heteroclitus
The Journal of Experimental Biology, 2016Co-Authors: Tara L Mcbryan, Timothy M Healy, Kristen L Haakons, Patricia M SchulteAbstract:Human activities are increasing both the frequency of hypoxic episodes and the mean temperature of aquatic ecosystems, but few studies have considered the possibility that acclimation to one of these stressors could improve the ability to cope with the other stressor. Here, we used Atlantic killifish, Fundulus heteroclitus, to test this hypothesis. Hypoxia tolerance was measured as time to loss of equilibrium in hypoxia (LOEhyp) at 0.4 kPa oxygen. Time to LOEhyp declined from 73.3 ± 6.9 min at 15 °C to 2.6 ± 3.8 min at 23 °C, and at 30 °C no fish could withstand this level of hypoxia. Prior acclimation to warm temperatures significantly increased time to LOEhyp. Hypoxia tolerance of the southern subspecies of killifish, F. heteroclitus heteroclitus, was greater than that of the northern subspecies, F. heteroclitus macrolepidotus, measured both as critical oxygen tension (Pcrit) and as time to LOEhyp. Warm acclimation offset the negative effects of temperature on time to LOEhyp to a similar extent in the two subspecies. Warm acclimation increased total lamellar surface area of the gill in both subspecies as a result of regression of an interlamellar cell mass (ILCM). However, differences in total lamellar surface area could not explain differences in time to LOEhyp between the subspecies, suggesting that the lower time to LOEhyp of northern fish is related to their higher routine metabolic rate. These data suggest that thermal plasticity in gill morphology can improve the capacity of this species to tolerate hypoxia, and shows how existing plasticity may help organisms to cope with the complex interacting stressors that they will encounter with increasing frequency as our climate changes.
Dawoon Jung - One of the best experts on this subject based on the ideXlab platform.
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expression of aquaporin 3 in gills of the atlantic killifish Fundulus heteroclitus effects of seawater acclimation
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2012Co-Authors: Dawoon Jung, Joseph R Shaw, Denry J Sato, Bruce A StantonAbstract:Estuarine fish, such as the Atlantic killifish (Fundulus heteroclitus), are constantly and rapidly exposed to changes in salinity. Although ion transport in killifish gills during acclimation to increased salinity has been studied extensively, no studies have examined the role of aquaglyceroporin 3 (AQP3), a water, glycerol, urea, and ammonia transporter, during acclimation to increased salinity in this sentinel environmental model organism. The goal of this study was to test the hypothesis that transfer from freshwater to seawater decreases AQP3 gene and protein expression in the gill of killifish. Transfer from freshwater to seawater decreased AQP3 mRNA in the gill after 1 day, but had no effect on total gill AQP3 protein abundance as determined by western blot. Quantitative confocal immunocytochemistry confirmed western blot studies that transfer from freshwater to seawater did not change total AQP3 abundance in the gill; however, immunocytochemistry revealed that the amount of AQP3 in pillar cells of secondary lamellae decreased in seawater fish, whereas the amount of AQP3 in mitochondrion rich cells (MRC) in primary filaments of the gill increased in seawater fish. This response of AQP3 expression is unique to killifish compared to other teleosts. Although the role of AQP3 in the gill of killifish has not been completely elucidated, these results suggest that AQP3 may play an important role in the ability of killifish to acclimate to increased salinity.
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genotoxicity in atlantic killifish Fundulus heteroclitus from a pah contaminated superfund site on the elizabeth river virginia
Ecotoxicology, 2011Co-Authors: Dawoon Jung, Cole W. Matson, Leonard B Collins, Geoff Laban, Heather M Stapleton, John W Bickham, James A Swenberg, Richard T. Di GiulioAbstract:The Atlantic Wood Industries Superfund site (AWI) on the Elizabeth River in Portsmouth, VA is heavily contaminated with polycyclic aromatic hydrocarbons (PAHs) from a wood treatment facility. Atlantic killifish, or mummichog (Fundulus heteroclitus), at this Superfund site are exposed to very high concentrations of several carcinogens. In this study, we measured PAH concentrations in both fish tissues and sediments. Concurrently, we assessed different aspects of genotoxicity in the killifish exposed in situ. Both sediment and tissue PAH levels were significantly higher in AWI samples, relative to a reference site, but the chemistry profile was different between sediments and tissues. Killifish at AWI exhibited higher levels of DNA damage compared to reference fish, as measured via the flow cytometric method (FCM), and the damage was consistent with sediment PAH concentrations. Covalent binding of benzo[a]pyrene (BaP) metabolites to DNA, as measured via LC–MS/MS adduct detection methods, were also elevated and could be partially responsible for the DNA damage. Using similar LC–MS/MS methods, we found no evidence that oxidative DNA adducts had a role in observed genotoxicity.
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ahr2 mediates cardiac teratogenesis of polycyclic aromatic hydrocarbons and pcb 126 in atlantic killifish Fundulus heteroclitus
Aquatic Toxicology, 2010Co-Authors: Bryan W. Clark, Dawoon Jung, Cole W. Matson, Richard T. Di GiulioAbstract:Exposure of developing fish to polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) results in a suite of defects including cardiac malformation, pericardial and yolk sac edema, craniofacial defects, and hemorrhaging. Several populations of Atlantic killifish or mummichog (Fundulus heteroclitus) on the Atlantic coast of the United States are resistant to the developmental and acute toxicity caused by PAHs and HAHs; this has made Fundulus a valuable model for studying aryl hydrocarbon sensitivity and adaptation. In order to further increase the utility of Fundulus, better understanding of the components of the molecular pathways governing aryl hydrocarbon response in Fundulus is required. The aryl hydrocarbon receptor (AHR) is known to mediate many of the toxic responses to PAHs and HAHs. A single AHR has been identified in mammals, but Fundulus has two AHRs and their relative roles are not clear. In the current study, translation-blocking and splice-junction morpholino gene knockdown was used to determine the roles of AHR1 and AHR2 in mediating cardiac teratogenesis induced by β-naphthoflavone (BNF), benzo[k]fluoranthene (BkF), and 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126). Here we report that AHR2 and not AHR1 knockdown resulted in rescue of teratogenicity induced by BNF, BkF, and PCB-126. These data demonstrate that AHR2 is the primary mediator of cardiac teratogenesis caused by multiple aryl hydrocarbons in Fundulus and suggest that suppression of the AHR pathway through modulation of AHR2 is a plausible mechanism for PAH resistance in adapted fish. Additionally, this is the first reported use of splice-junction morpholinos in Fundulus.
Marjorie F Oleksiak - One of the best experts on this subject based on the ideXlab platform.
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evolutionary physiology and genomics in the highly adaptable killifish Fundulus heteroclitus
Comprehensive Physiology, 2020Co-Authors: Douglas L Crawford, Patricia M Schulte, Marjorie F OleksiakAbstract:By investigating evolutionary adaptations that change physiological functions, we can enhance our understanding of how organisms work, the importance of physiological traits, and the genes that influence these traits. This approach of investigating the evolution of physiological adaptation has been used with the teleost fish Fundulus heteroclitus and has produced insights into (i) how protein polymorphisms enhance swimming and development; (ii) the role of equilibrium enzymes in modulating metabolic flux; (iii) how variation in DNA sequences and mRNA expression patterns mitigate changes in temperature, pollution, and salinity; and (iv) the importance of nuclear-mitochondrial genome interactions for energy metabolism. Fundulus heteroclitus provides so many examples of adaptive evolution because their local population sizes are large, they have significant standing genetic variation, and they experience large ranges of environmental conditions that enhance the likelihood that adaptive evolution will occur. Thus, F. heteroclitus research takes advantage of evolutionary changes associated with exposure to diverse environments, both across the North American Atlantic coast and within local habitats, to contrast neutral versus adaptive divergence. Based on evolutionary analyses contrasting neutral and adaptive evolution in F. heteroclitus populations, we conclude that adaptive evolution can occur readily and rapidly, at least in part because it depends on large amounts of standing genetic variation among many genes that can alter physiological traits. These observations of polygenic adaptation enhance our understanding of how evolution and physiological adaptation progresses, thus informing both biological and medical scientists about genotype-phenotype relationships. © 2020 American Physiological Society. Compr Physiol 10:637-671, 2020.
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effects of anthropogenic pollution on the oxidative phosphorylation pathway of hepatocytes from natural populations of Fundulus heteroclitus
Aquatic Toxicology, 2015Co-Authors: Douglas L Crawford, Marjorie F OleksiakAbstract:Abstract Persistent organic pollutants (POPs), including polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), potentially target mitochondria and cause toxicity. We compared the effects of POPs on mitochondrial respiration by measuring oxidative phosphorylation (OxPhos) metabolism in hepatocytes isolated from lab-depurated Fundulus heteroclitus from a Superfund site contaminated with PAHs (Elizabeth River VA, USA) relative to OxPhos metabolism in individuals from a relatively clean, reference population (King’s Creek VA, USA). In individuals from the polluted Elizabeth River population, OxPhos metabolism displayed lower LEAK and lower activities in complex III, complex IV, and E State, but higher activity in complex I compared to individuals from the reference King’s Creek population. To test the supposition that these differences were due to or related to the chronic PAH contamination history of the Elizabeth River population, we compared the OxPhos functions of undosed individuals from the polluted and reference populations to individuals from these populations dosed with a PAH {benzo [α] pyrene (BaP)} or a PCB {PCB126 (3,3′,4,4′,5-pentachlorobiphenyl)}, respectively. Exposure to PAH or PCB affected OxPhos in the reference King’s Creek population but had no detectable effects on the polluted Elizabeth River population. Thus, PAH exposure significantly increased LEAK, and exposure to PCB126 significantly decreased State 3, E state and complex I activity in the reference King’s Creek population. These data strongly implicate an evolved tolerance in the Elizabeth River fish where dosed fish are not affected by PAH exposure and undosed fish show decreased LEAK and increased State 3 and E state.
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phenotypic plasticity in gene expression contributes to divergence of locally adapted populations of Fundulus heteroclitus
Molecular Ecology, 2015Co-Authors: David I Dayan, Douglas L Crawford, Marjorie F OleksiakAbstract:We examine the interaction between phenotypic plasticity and evolutionary adaptation using muscle gene expression levels among populations of the fish Fundulus heteroclitus acclimated to three temperatures. Our analysis reveals shared patterns of phenotypic plasticity due to thermal acclimation as well as non-neutral patterns of variation among populations adapted to different thermal environments. For the majority of significant differences in gene expression levels, phenotypic plasticity and adaptation operate on different suites of genes. The subset of genes that demonstrate both adaptive differences and phenotypic plasticity, however, exhibit countergradient variation of expression. Thus, expression differences among populations counteract environmental effects, reducing the phenotypic differentiation between populations. Finally, gene-by-environment interactions among genes with non-neutral patterns of expression suggest that the penetrance of adaptive variation depends on the environmental conditions experienced by the individual.
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transcriptomic assessment of resistance to effects of an aryl hydrocarbon receptor ahr agonist in embryos of atlantic killifish Fundulus heteroclitus from a marine superfund site
BMC Genomics, 2011Co-Authors: Marjorie F Oleksiak, Matthew J. Jenny, Sibel I Karchner, Diana G Franks, David Mark B Welch, Mark E HahnAbstract:Background Populations of Atlantic killifish (Fundulus heteroclitus) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A), a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. We compared gene expression profiles and the response to 3,3',4,4',5-pentachlorobiphenyl (PCB-126) exposure in embryos (5 and 10 dpf) and larvae (15 dpf) from F. heteroclitus populations inhabiting the New Bedford Harbor, Massachusetts (NBH) Superfund site (PCB-resistant) and a reference site, Scorton Creek, Massachusetts (SC; PCB-sensitive).
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natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus
Nature Genetics, 2005Co-Authors: Marjorie F Oleksiak, Jennifer L Roach, Douglas L CrawfordAbstract:Individual variation in gene expression is important for evolutionary adaptation1,2 and susceptibility to diseases and pathologies3,4. In this study, we address the functional importance of this variation by comparing cardiac metabolism to patterns of mRNA expression using microarrays. There is extensive variation in both cardiac metabolism and the expression of metabolic genes among individuals of the teleost fish Fundulus heteroclitus from natural outbred populations raised in a common environment: metabolism differed among individuals by a factor of more than 2, and expression levels of 94% of genes were significantly different (P < 0.01) between individuals in a population. This unexpectedly high variation in metabolic gene expression explains much of the variation in metabolism, suggesting that it is biologically relevant. The patterns of gene expression that are most important in explaining cardiac metabolism differ between groups of individuals. Apparently, the variation in metabolism seems to be related to different patterns of gene expression in the different groups of individuals. The magnitude of differences in gene expression in these groups is not important; large changes in expression have no greater predictive value than small changes. These data suggest that variation in physiological performance is related to the subtle variation in gene expression and that this relationship differs among individuals.
Diane Nacci - One of the best experts on this subject based on the ideXlab platform.
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developing a high quality linkage map for the atlantic killifish Fundulus heteroclitus
G3: Genes Genomes Genetics, 2019Co-Authors: Jeffrey T Miller, Diane Nacci, Noah M Reid, Andrew WhiteheadAbstract:Killifish (Fundulus heteroclitus) are widely distributed among different aquatic environments where they demonstrate an impressive range of highly-plastic and locally adaptive phenotypes. High-throughput sequencing has begun to unravel the mechanisms and evolutionary history of these interesting features by establishing relationships in the genotype-phenotype map. However, some genotype-phenotype analyses require a higher order of contiguity than what initial scaffolded (fragmented genome assembly where contigs have been assemble into scaffolds) genome assemblies can provide. Here, we used 5,685 high-quality RAD-Seq markers from a single mapping family to order 84% of the scaffolded genome assembly to 24 chromosomes. This serves to: 1) expand the killifish genomic toolkit, 2) estimate genome-wide recombination rates, and 3) compare genome synteny to humans and other fishes. After initially building our map, we found that the selection of thresholds for sequence data filtration highly impacted scaffold placement in the map. We outline each step of the approach that dramatically improved our map to help guide others toward more effective linkage mapping for genome assembly. Our final map supports strong conservation of genomic synteny among closely related fish species and reveals previously described chromosomal rearrangements between more distantly related clades. However, we also commonly found minor scaffold misorientations in F. heteroclitus and in other assemblies, suggesting that further mapping (such as optical mapping) is necessary for finer scale resolution of genome structure. Lastly, we discuss the problems that would be expected from misoriented/unplaced scaffolds and stress the importance of a quality mapped genome as a key feature for further investigating population and comparative genomic questions with F. heteroclitus and other taxa.
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genetic diversity and structure of an estuarine fish Fundulus heteroclitus indigenous to sites associated with a highly contaminated urban harbor
Ecotoxicology, 2006Co-Authors: Amy M Mcmillan, Mark J Bagley, Suzanne A Jackson, Diane NacciAbstract:Intense selection on isolated populations can cause loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that polychlorinated biphenyls (PCBs), have acted as strong selective agents on populations of a non-migratory fish, Fundulus heteroclitus, indigenous to heavily contaminated sites. To evaluate population genetic structure and test for effects of intense, multi-generational PCB contamination on genetic diversity, we used AFLP analysis on fish collected from six sites along the east coast of North America that varied widely in PCB contamination. The sites included a heavily contaminated urban harbor (New Bedford, MA), an adjacent moderately contaminated sub-estuary (Buzzards Bay, MA), and an uncontaminated estuary 60 km away (Narragansett, RI). AFLP markers distinguished populations at moderate and small scales, suggesting genetic differentiation at distances of 2 km or less. Genetic diversity did not differ across the study sites. Genome-wide diversity may have been preserved because of large effective population sizes and/or because the mechanism for genetic adaptation to these contaminants affected only a small number of loci. Alternatively, loss in diversity may have been restored with moderate levels of migration and relatively short generation time for this species.
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cytochrome p4501a cyp1a in killifish Fundulus heteroclitus heritability of altered expression and relationship to survival in contaminated sediments
Toxicological Sciences, 2002Co-Authors: Joel N Meyer, Diane Nacci, Richard T. Di GiulioAbstract:Previous research has shown that killifish (Fundulus heteroclitus) inhabiting a creosote-contaminated site on the Elizabeth River in Virginia exhibit little induction of cytochrome P4501A (CYP1A) protein expression and activity upon exposure to typical CYP1A-inducing chemicals. We characterized the CYP1A response of first, second, and third generation laboratory-raised offspring of feral Elizabeth River killifish to exposure to sediments from the contaminated site as well as the prototypical polycyclic aromatic hydrocarbon (PAH)-type CYP1A inducers beta-naphthoflavone (BNF) and 3-methylcholanthrene (3-MC). The Elizabeth River offspring's responses were compared to those of offspring of killifish from two reference sites (King's Creek, Virginia, and Russell Creek, North Carolina). As with feral Elizabeth River killifish, the first generation embryos and larvae were refractory to CYP1A induction. However, the response observed in 3-year-old first generation adults, as well as with second and third generation fish, was much closer to that observed in reference-site fish. We suggest that the pattern of altered CYP1A response in Elizabeth River killifish, while persistent and heritable for one generation, is mostly nongenetically based. Additionally, we investigated the hypothesis that low CYP1A activity (measured as in ovo EROD activity) would correlate to increased survival in Elizabeth River sediment pore water; this hypothesis was not supported by our results.
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adaptations of wild populations of the estuarine fish Fundulus heteroclitus to persistent environmental contaminants
Marine Biology, 1999Co-Authors: Diane Nacci, Laura Coiro, Saro Jayaraman, Rick Mckinney, Timothy R Gleason, Wayne R Munns, Jennifer L Specker, Keith R CooperAbstract:Many aquatic species, including the estuarine fish Fundulus heteroclitus (mummichogs), adapt to local environmental conditions. We conducted studies to evaluate whether highly exposed populations of mummichogs adapt to toxic environmental contaminants. These fish populations are indigenous to an urban estuary contaminated with persistent and bioaccumulative contaminants (dioxin-like compounds, or DLCs) that are particularly toxic to the early development of fish. We conducted laboratory challenge experiments to compare mummichog embryos and larvae from reference sites and this highly contaminated site [New Bedford Harbor (NBH), Massachusetts, USA] for their sensitivity to DLCs. While there was variation in DLC-responsiveness within each group, fish from NBH were profoundly less sensitive to DLCs than reference fish. Specifically, concentrations of DLCs similar to those measured in NBH-collected mummichog eggs were lethal to reference embryos. Further, DLC-responsiveness was inherited and independent of maternal contaminant contributions. These findings are consistent with the conclusion that DLC contamination in NBH has contributed to the selection of fish that are resistant to the short-term toxic effects of these environmental-contaminant exposures. This adaptation may be a critical mechanism by which fish populations persist in this highly contaminated site. Further evaluation of this ecosystem may provide important information concerning the direct and indirect consequences of this “unnatural” selection.
