小柯机器人

美国加州大学旧金山分校Hiten D. Madhani研究组发现，古老物种中从头甲基转移酶丢失后，DNA甲基化的进化持久性已存在数百万年。这一研究成果于2020年1月16日在线发表在国际学术期刊《细胞》上。

研究人员发现，Dnmt5在体外和体内显示出精确的维持型特异性，并如同后生生物的维持甲基化酶Dnmt1，利用相似的体内辅因子。值得注意的是，系统发育和功能分析表明，这一古老物种失去了一种新的甲基化酶DnmtX的基因，介于50-150百万年前之间。研究人员检查了古老物种中DnmtX丢失以来甲基化如何持续存在。实验和比较研究表明，新生隐球菌中甲基化模式的有效复制、罕见的随机甲基化损失和获得事件以及自然选择的作用。研究人员认为，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。

据介绍，DNA的胞嘧啶甲基化是DNA的广泛修饰，起着许多关键作用。在酵母新生隐球菌中，CG甲基化发生在富含转座子的重复序列中，需要DNA甲基转移酶Dnmt5。

附：英文原文

Title: Evolutionary Persistence of DNA Methylation for Millions of Years after Ancient Loss of a De Novo Methyltransferase

Author: Sandra Catania, Phillip A. Dumesic, Harold Pimentel, Ammar Nasif, Caitlin I. Stoddard, Jordan E. Burke, Jolene K. Diedrich, Sophie Cook, Terrance Shea, Elizabeth Geinger, Robert Lintner, John R. Yates, Petra Hajkova, Geeta J. Narlikar, Christina A. Cuomo, Jonathan K. Pritchard, Hiten D. Madhani

Issue&Volume: January 16, 2020

Abstract: Cytosine methylation of DNA is a widespread modification of DNA that plays numerouscritical roles. In the yeast Cryptococcus neoformans, CG methylation occurs in transposon-rich repeats and requires the DNA methyltransferaseDnmt5. 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 andfunctional 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 sincethe ancient loss of DnmtX. Experimental and comparative studies reveal efficient replicationof 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 processanalogous to Darwinian evolution of the genome.

DOI: 10.1016/j.cell.2019.12.012

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31374-1