Marine Biological Laboratory, Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Woods Hole, Massachusetts, USA.
Bioessays. 2023 Jul;45(7):e2200232. doi: 10.1002/bies.202200232.
DNA methylation constitutes one of the pillars of epigenetics, relying on covalent bonds for addition and/or removal of chemically distinct marks within the major groove of the double helix. DNA methyltransferases, enzymes which introduce methyl marks, initially evolved in prokaryotes as components of restriction-modification systems protecting host genomes from bacteriophages and other invading foreign DNA. In early eukaryotic evolution, DNA methyltransferases were horizontally transferred from bacteria into eukaryotes several times and independently co-opted into epigenetic regulatory systems, primarily via establishing connections with the chromatin environment. While C5-methylcytosine is the cornerstone of plant and animal epigenetics and has been investigated in much detail, the epigenetic role of other methylated bases is less clear. The recent addition of N4-methylcytosine of bacterial origin as a metazoan DNA modification highlights the prerequisites for foreign gene co-option into the host regulatory networks, and challenges the existing paradigms concerning the origin and evolution of eukaryotic regulatory systems.
DNA 甲基化是表观遗传学的基石之一，它依赖于双螺旋大沟内的共价键，来添加和/或去除化学性质不同的标记。最初，作为限制-修饰系统的组成部分，将甲基标记引入 DNA 的 DNA 甲基转移酶在原核生物中进化，该系统保护宿主基因组免受噬菌体和其他入侵的外源 DNA 的侵害。在早期的真核生物进化过程中，DNA 甲基转移酶通过水平基因转移多次从细菌转移到真核生物中，并独立地被重新用于表观遗传调控系统，主要是通过与染色质环境建立联系。虽然 C5-甲基胞嘧啶是植物和动物表观遗传学的基石，并已被详细研究，但其他甲基化碱基的表观遗传作用尚不清楚。最近，细菌来源的 N4-甲基胞嘧啶被添加为后生动物的 DNA 修饰，这突出了外源基因被纳入宿主调控网络的先决条件，并挑战了关于真核调控系统起源和进化的现有范例。
