Jiang Cizhong, Han Leng, Su Bing, Li Wen-Hsiung, Zhao Zhongming
Department of Psychiatry and Center for the Study of Biological Complexity, Virginia Commonwealth, USA.
Mol Biol Evol. 2007 Sep;24(9):1991-2000. doi: 10.1093/molbev/msm128. Epub 2007 Jun 24.
CpG islands (CGIs) are often considered as gene markers, but the number of CGIs varies among mammalian genomes that have similar numbers of genes. In this study, we investigated the distribution of CGIs in the promoter regions of 3,197 human-mouse orthologous gene pairs and found that the mouse genome has notably fewer CGIs in the promoter regions and less pronounced CGI characteristics than does the human genome. We further inferred CGI's ancestral state using the dog genome as a reference and examined the nucleotide substitution pattern and the mutational direction in the conserved regions of human and mouse CGIs. The results reveal many losses of CGIs in both genomes but the loss rate in the mouse lineage is two to four times the rate in the human lineage. We found an intriguing feature of CGI loss, namely that the loss of a CGI usually starts from erosion at the both edges and gradually moves towards the center. We found functional bias in the genes that have lost promoter-associated CGIs in the human or mouse lineage. Finally, our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated. Our study provides a detailed view of the evolution of promoter-associated CGIs in the human and mouse genomes and our findings are helpful for understanding the evolution of mammalian genomes and the role of CGIs in gene function.
CpG岛（CGIs）通常被视为基因标记，但在基因数量相似的哺乳动物基因组中，CGIs的数量存在差异。在本研究中，我们调查了3197对人鼠直系同源基因对启动子区域中CGIs的分布，发现小鼠基因组启动子区域中的CGIs明显少于人类基因组，且CGI特征也不如人类基因组明显。我们以狗基因组为参考进一步推断CGI的祖先状态，并研究了人类和小鼠CGIs保守区域的核苷酸替换模式和突变方向。结果显示，两个基因组中都有许多CGIs丢失，但小鼠谱系中的丢失率是人类谱系的两到四倍。我们发现了CGI丢失的一个有趣特征，即CGI的丢失通常从两端的侵蚀开始，并逐渐向中心移动。我们在人类或小鼠谱系中失去启动子相关CGIs的基因中发现了功能偏差。最后，我们的分析表明，CGIs与管家基因的关联并不像之前估计的那么强。我们的研究详细阐述了人类和小鼠基因组中启动子相关CGIs的进化情况，我们的发现有助于理解哺乳动物基因组的进化以及CGIs在基因功能中的作用。
