Data from: Inbreeding effects on gene-specific DNA methylation among tissues of Chinook salmon
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Inbreeding depression is the loss of fitness resulting from the mating of genetically-related individuals. Traditionally, the study of inbreeding depression focused on genetic effects, though recent research has identified DNA methylation as also having a role in inbreeding effects. Since inbreeding depression and DNA methylation change with age and environmental stress, DNA methylation is a likely candidate for the regulation of genes associated with inbreeding depression. Here we use a targeted, multi-gene approach to assess methylation at 22 growth, metabolic, immune, and stress-related genes. We developed PCR-based DNA methylation assays to test the effects of intense inbreeding on intragenic gene-specific methylation in inbred and outbred Chinook salmon. Inbred fish had altered methylation at three genes, CK-1, GTIIBS, and hsp70, suggesting that methylation changes associated with inbreeding depression are targeted to specific genes and are not whole-genome effects. While we did not find a significant inbreeding by age interaction, we found that DNA methylation generally increases with age, though methylation decreased with age in five genes, CK-1, IFNɣ, HNRNP, hsc71, and FSHb, potentially due to environmental context and sexual maturation. As expected, we found methylation patterns differed among tissue types, highlighting the need for careful selection of target tissue for methylation studies. This study provides insight into the role of epigenetic effects on aging, environment and tissue function in Chinook salmon and shows that methylation is a targeted and regulated cellular process. We provide the first evidence of epigenetically-based inbreeding depression in vertebrates.
近交衰退(inbreeding depression)指遗传相关个体交配所导致的适合度下降。传统上,近交衰退的研究聚焦于遗传效应,不过近期研究发现DNA甲基化(DNA methylation)同样在近交效应中发挥作用。由于近交衰退与DNA甲基化均会随年龄和环境胁迫发生变化,DNA甲基化极有可能是调控与近交衰退相关基因的候选机制。本研究采用靶向多基因研究方法,对22个与生长、代谢、免疫及胁迫相关的基因的甲基化水平进行评估。我们开发了基于聚合酶链式反应(PCR)的DNA甲基化检测手段,以探究高强度近交对奇努克鲑鱼(Chinook salmon)近交组与远交组个体的基因内区域基因特异性甲基化的影响。研究发现,近交个体在CK-1、GTIIBS与hsp70三个基因上的甲基化水平发生改变,这表明与近交衰退相关的甲基化变化具有基因靶向性,并非全基因组范围的效应。尽管未发现近交与年龄的显著交互作用,但我们观察到DNA甲基化整体随年龄上升,不过CK-1、IFNɣ、HNRNP、hsc71及FSHb这5个基因的甲基化水平却随年龄降低,这一现象可能与环境背景及性成熟过程相关。正如预期,不同组织类型间的甲基化模式存在差异,这凸显了甲基化研究中谨慎选择靶组织的必要性。本研究揭示了表观遗传效应在奇努克鲑鱼衰老、环境响应及组织功能中的作用,并证实甲基化是一种具有靶向性且受调控的细胞过程。我们首次为脊椎动物中基于表观遗传机制的近交衰退提供了证据。



