Atlantic killifish inhabiting polluted sites along the east coast of the U.S. have evolved resistance to toxic effects of contaminants. One such contaminated site is the Acushnet River estuary, near New Bedford Harbor (NBH), Massachusetts, which is characterized by very high PCB concentrations in the sediments and in the tissues of resident killifish. Though killifish at this site appear to be thriving, the metabolic costs of survival in a highly contaminated environment are not well understood. In this study we compared the hepatic metabolite profiles of resistant (NBH) and sensitive populations (Scorton Creek (SC), Sandwich, MA) using a targeted metabolomics approach in which polar metabolites were extracted from adult fish livers and quantified. Our results revealed differences in the levels of several metabolites between fish from the two sites. The majority of these metabolites are associated with one-carbon metabolism, an important pathway that supports multiple physiological processes including DNA and protein methylation, nucleic acid biosynthesis and amino acid metabolism. We measured the gene expression of DNA methylation (DNA methyltransferase 1, dnmt1) and demethylation genes (Ten-Eleven Translocation (TET) genes) in the two populations, and observed lower levels of dnmt1 and higher levels of TET gene expression in the NBH livers, suggesting possible differences in DNA methylation profiles. Consistent with this, the two populations differed significantly in the levels of 5-methylcytosine and 5-hydroxymethylcytosine nucleotides. Overall, our results suggest that the unique hepatic metabolite signatures observed in NBH and SC reflect the adaptive mechanisms for survival in their respective habitats.

栖息在美国东海岸受污染地点的大西洋鳉鱼已经进化出对污染物毒性作用的抵抗力。此类受污染地点之一是马萨诸塞州新贝德福德港 (NBH) 附近的 Acushnet 河河口，其特点是沉积物中和常住鳉鱼组织中的 PCB 浓度非常高。尽管该地点的鳉鱼似乎很繁荣，但人们对在高度污染的环境中生存的代谢成本尚不清楚。在这项研究中，我们使用靶向代谢组学方法比较了抗性 (NBH) 和敏感种群（Scorton Creek (SC)，马萨诸塞州三明治）的肝脏代谢物谱，其中极性代谢物从成鱼肝脏中提取并量化。我们的结果揭示了来自两个地点的鱼之间几种代谢物水平的差异。大多数这些代谢物与一碳代谢相关，这是一种支持多种生理过程的重要途径，包括 DNA 和蛋白质甲基化、核酸生物合成和氨基酸代谢。我们测量了 DNA 甲基化的基因表达（DNA 甲基转移酶 1、dnmt1）和去甲基化基因（十一个十一易位（TET）基因），并观察到NBH 肝脏中较低水平的dnmt1和较高水平 TET 基因表达，表明 DNA 甲基化谱可能存在差异。与此一致，这两个群体在 5-甲基胞嘧啶和 5-羟甲基胞嘧啶核苷酸的水平上存在显着差异。总体而言，我们的结果表明，在 NBH 和 SC 中观察到的独特肝脏代谢物特征反映了在其各自栖息地中生存的适应性机制。