Human Genome Centre, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
BMC Genomics. 2011 Nov 30;12 Suppl 3(Suppl 3):S7. doi: 10.1186/1471-2164-12-S3-S7.
CpG islands are observed in mammals and other vertebrates, generally escape DNA methylation, and tend to occur in the promoters of widely expressed genes. Another class of promoter has lower G+C and CpG contents, and is thought to be involved in the spatiotemporal regulation of gene expression. Non-vertebrate deuterostomes are reported to have a single class of promoter with high-frequency CpG dinucleotides, suggesting that this is the original type of promoter. However, the limited annotation of these genes has impeded the large-scale analysis of their promoters.
To determine the origins of the two classes of vertebrate promoters, we chose Ciona intestinalis, an invertebrate that is evolutionarily close to the vertebrates, and identified its transcription start sites genome-wide using a next-generation sequencer. We indeed observed a high CpG content around the transcription start sites, but their levels in the promoters and background sequences differed much less than in mammals. The CpG-rich stretches were also fairly restricted, so they appeared more similar to mammalian CpG-poor promoters.
From these data, we infer that CpG islands are not sufficiently ancient to be found in invertebrates. They probably appeared early in vertebrate evolution via some active mechanism and have since been maintained as part of vertebrate promoters.
CpG 岛存在于哺乳动物和其他脊椎动物中,通常逃避 DNA 甲基化,并且倾向于出现在广泛表达的基因的启动子中。另一类启动子具有较低的 G+C 和 CpG 含量,被认为参与基因表达的时空调节。已报道非脊椎后口动物具有具有高频 CpG 二核苷酸的单一类型启动子,表明这是原始类型的启动子。然而,这些基因的有限注释阻碍了对其启动子的大规模分析。
为了确定两种脊椎动物启动子的起源,我们选择了与脊椎动物进化关系密切的无脊椎动物 Ciona intestinalis,并使用下一代测序仪在全基因组范围内鉴定其转录起始位点。我们确实在转录起始位点周围观察到高 CpG 含量,但它们在启动子和背景序列中的水平差异远小于哺乳动物。富含 CpG 的片段也相当受限,因此它们与哺乳动物的 CpG 贫乏启动子更为相似。
从这些数据中,我们推断 CpG 岛在无脊椎动物中不够古老。它们可能在脊椎动物进化的早期通过某种主动机制出现,并且此后一直作为脊椎动物启动子的一部分得到维持。