Major gene expression changes and epigenetic remodelling in Nile tilapia muscle after just one generation of domestication

The historically recent domestication of fishes has been essential to meet the protein demands of a growing human population. Selection for traits of interest during domestication is a complex process whose epigenetic basis is poorly understood. Cytosine hydroxymethylation is increasingly recognized as an important DNA modification involved in epigenetic regulation. In the present study, we investigated if hydroxymethylation plays a role in fish domestication and demonstrated for the first time at a genome-wide level and single nucleotide resolution that the muscle hydroxymethylome changes after a single generation of Nile tilapia (Oreochromis niloticus, Linnaeus) domestication. The overall decrease in hydroxymethylcytosine levels was accompanied by the downregulation of 2015 genes in fish reared in captivity compared to their wild progenitors. In contrast, several myogenic and metabolic genes that can affect growth potential were upregulated. There were 126 differentially hydroxymethylated cytosines between groups, which were not due to genetic variation; they were associated with genes involved in immune-, growth- and neuronal-related pathways. Taken together, our data unveil a new role for DNA hydroxymethylation in epigenetic regulation of fish domestication with impact in aquaculture and implications in artificial selection, environmental adaptation and genome evolution.

为满足日益增长的全球人口对蛋白质的需求，近年来开展的鱼类驯化工作至关重要。驯化过程中针对目标性状的选育是一个复杂过程，其表观遗传基础至今仍未被充分阐明。胞嘧啶羟甲基化（Cytosine hydroxymethylation）作为参与表观遗传调控的重要DNA修饰方式，正得到学界越来越多的认可。本研究探究了羟甲基胞嘧啶修饰在鱼类驯化过程中是否发挥作用，并首次在全基因组水平与单核苷酸分辨率下证实：仅经过一代驯化的尼罗罗非鱼（Oreochromis niloticus, Linnaeus）的肌肉组织羟甲基化组（hydroxymethylome）发生了显著改变。与野生亲本相比，人工养殖的尼罗罗非鱼其羟甲基胞嘧啶水平整体下降，同时伴随2015个基因的表达下调；与之相反，若干可影响生长潜能的肌源性与代谢相关基因则出现表达上调。两组间存在126个差异羟甲基化胞嘧啶位点，且该差异并非由遗传变异所致；这些位点与免疫、生长及神经元相关通路所涉及的基因存在关联。综上，本研究数据揭示了DNA羟甲基化在鱼类驯化表观遗传调控中的全新作用，该发现对水产养殖具有重要应用价值，同时为人工选择、环境适应以及基因组进化相关研究提供了新的启示。