National Observation and Research Station for Yangtze Estuarine Wetland Ecosystems, and Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Institute of Biodiversity Science, Fudan University, Shanghai 200438, China.
Redpath Museum and Department of Biology, McGill University, Montreal, QC H3A 0C4, Canada.
Genetics. 2021 Mar 3;217(1):1-15. doi: 10.1093/genetics/iyab001.
Epigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24-35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.
表型变化的表观遗传机制被假设为在面对环境变化时有助于种群的持续和适应。迄今为止，很少有研究探索自然种群中世代间稳定甲基化水平的遗传性，并且对于顺式和反式调控变化对甲基化变异的相对贡献知之甚少。在这里，我们探索了 DNA 甲基化的遗传性，并进行了甲基化数量性状基因座（meQTL）分析，以研究三刺鱼（Gasterosteus aculeatus）海洋和淡水生态型之间甲基化变异的遗传结构。我们使用 F1 和 F2 杂交及其海洋和淡水来源种群的简化重亚硫酸盐测序技术，在鳍组织中定量测量了全基因组 DNA 甲基化。我们确定了在几代之间表现出稳定甲基化水平的胞嘧啶（CpG 位点）。我们发现，加性遗传方差平均解释了 24-35%的甲基化方差，其中一些 CpG 位点可能不受遗传控制。我们还检测到顺式和反式 meQTL，只有反式 meQTL 与海洋和淡水生态型之间高度分化的先前鉴定的基因组区域重叠。最后，我们确定了两个关键 CpG 位点的遗传结构，这些位点在生态型之间存在差异甲基化。这些发现表明 DNA 甲基化在促进对不同环境的适应方面可能发挥作用，并提高了我们对种群表观基因组变异的可遗传性基础的理解。
