Cytosine methylation of DNA is a widespread modification of DNA that plays numerous critical roles. In the yeast Cryptococcus neoformans, CG methylation occurs in transposon-rich repeats and requires the DNA methyltransferase Dnmt5. We show that Dnmt5 displays exquisite maintenance-type specificity in vitro and in vivo and utilizes similar in vivo cofactors as the metazoan maintenance methylase Dnmt1. Remarkably, phylogenetic and functional analysis revealed that the ancestral species lost the gene for a de novo methylase, DnmtX, between 50-150 mya. We examined how methylation has persisted since the ancient loss of DnmtX. Experimental and comparative studies reveal efficient replication of methylation patterns in C. neoformans, rare stochastic methylation loss and gain events, and the action of natural selection. We propose that an epigenome has been propagated for >50 million years through a process analogous to Darwinian evolution of the genome.

中文翻译：

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在古老的从头甲基转移酶缺失后，DNA 甲基化的进化持续了数百万年。

DNA 胞嘧啶甲基化是一种广泛的 DNA 修饰，发挥着许多关键作用。在酵母新型隐球菌中，CG 甲基化发生在富含转座子的重复序列中，并且需要 DNA 甲基转移酶 Dnmt5。我们表明，Dnmt5 在体外和体内表现出精致的维持型特异性，并利用与后生动物维持甲基化酶 Dnmt1 相似的体内辅因子。值得注意的是，系统发育和功能分析表明，祖先物种在 50-150 mya 之间丢失了从头甲基化酶 DnmtX 的基因。我们研究了自 DnmtX 古代缺失以来甲基化是如何持续存在的。实验和比较研究揭示了新型隐球菌中甲基化模式的有效复制、罕见的随机甲基化丢失和获得事件以及自然选择的作用。我们认为表观基因组已经通过类似于达尔文基因组进化的过程传播了超过 5000 万年。