背景:5-甲基胞嘧啶(5mC)形式的DNA甲基化是动物中最丰富的碱基修饰。然而,5mC水平在分类群之间差异很大。虽然脊椎动物基因组是高度甲基化的,在大多数无脊椎动物中,5mC专注于持续和高度转录的基因(基因体甲基化;GbM),在某些物种中,在转座因子(TE)上,一种被称为“马赛克”的图案。然而,5mC的作用和发育动力学以及这些如何解释DNA甲基化模式中的种间差异仍然知之甚少,尤其是在Spiralia,一大片无脊椎动物进化枝,占动物门的近一半。
结果:这里,我们在Annelida中生成具有不同基因组特征和系统发育位置的三个物种的碱基分辨率甲基化组,一个主要的螺旋体门。所有可能的5mC模式都发生在环节动物中,从镶嵌分布中典型的无脊椎动物中等水平到超甲基化和甲基化损失。GbM对于具有5mC的环节动物是常见的,物种间的甲基化差异可以通过分类单元特异性转录动力学或内含子TE的存在来解释。值得注意的是,GbM和转录之间的联系在发育过程中衰减,伴随着一个渐进的和全球性的,成年阶段的年龄依赖性去甲基化。此外,在早期发育过程中,用胞苷类似物降低5mC水平会损害正常的胚胎发生,并重新激活类卵形Owenia中的TE。
结论:我们的研究表明,发育和衰老过程中的整体表观遗传侵蚀是双侧动物的祖先特征。然而,转录和基因体甲基化之间的紧密联系在早期胚胎阶段可能更重要,5mC介导的TE沉默可能在动物谱系中出现。
BACKGROUND: DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as \"mosaic\". Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla.
RESULTS: Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis.
CONCLUSIONS: Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.