Bird A P
Institute of Cell and Molecular Biology, University of Edinburgh, United Kingdom.
Cold Spring Harb Symp Quant Biol. 1993;58:281-5. doi: 10.1101/sqb.1993.058.01.033.
DNA methylation is ancestrally a mechanism for neutralizing potentially damaging DNA elements in the genome. The genomes of most multicellular organisms contain a small fraction of methylated DNA that contains the methylated elements, whereas the organism's own genes remain free of methylation. Vertebrates are exceptional among animals in that their genomes, including genes, are predominantly methylated. They retain the ability to inactivate viral DNA but have recruited the DNA methylation system for new functions. Widespread low-density methylation can contribute to lowering of the level of transcriptional "noise" from cryptic or inappropriate promoters. This may be the major advantage of DNA methylation in these organisms and may be sufficiently beneficial to offset the disadvantage of m5C mutability. The other novel feature of DNA methylation in vertebrates is the capacity to de novo methylate certain CpG islands, causing long-term strong repression. These evolutionary innovations may explain the high complexity of vertebrate organs and cell types.
从进化角度来看，DNA甲基化是一种使基因组中潜在有害的DNA元件失活的机制。大多数多细胞生物的基因组中含有一小部分甲基化DNA，其中包含甲基化元件，而生物体自身的基因则保持未甲基化状态。脊椎动物在动物中是例外，因为它们的基因组，包括基因，主要是甲基化的。它们保留了使病毒DNA失活的能力，但已将DNA甲基化系统用于新的功能。广泛的低密度甲基化有助于降低来自隐蔽或不适当启动子的转录“噪音”水平。这可能是这些生物体中DNA甲基化的主要优势，并且可能足以抵消5-甲基胞嘧啶（m5C）易变性的劣势。脊椎动物DNA甲基化的另一个新特征是能够对某些CpG岛进行从头甲基化，从而导致长期的强烈抑制。这些进化创新可能解释了脊椎动物器官和细胞类型的高度复杂性。
