脊椎动物进化早期基因组DNA甲基化模式进化及其功能研究

项目名称： 脊椎动物进化早期基因组DNA甲基化模式进化及其功能研究

项目编号： No.31272299

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 苏志熙

作者单位： 复旦大学

项目金额： 83万元

中文摘要： DNA甲基化（DM）是一种重要的表观遗传学机制，参与多种生物过程的调控，它的失调能导致癌症等多种疾病。现已有超过 20 种真核生物的甲基化组已被测序，促进了我们对其进化模式和功能的认识。但是由于缺少从无脊椎动物到脊椎动物进化边缘的关键物种的信息，我们对DM模式在这一阶段的进化过程和功能还了解的很少。例如我们对DM从镶嵌式到全局化模式的进化过程是不是渐变的还有很大争议；对DM调控与早期脊椎动物基因表达调控进化的关系也知之甚少。为解答这些问题，我们计划利用二代测序的方法测定海七鳃鳗心脏和脑组织的甲基化组，mRNA和miRNA转录组，以及玻璃海鞘的心脏和脑的mRNA和miRNA转录组。结合已发表的数据，我们将探究基因组DM模式在脊椎动物进化早期的变化过程；DM模式改变对基因表达的影响；提出并验证脊椎动物复杂性进化的表观调控假说。这一研究将有助于更深入的了解DM的调控机制及功能。

中文关键词： DNA 甲基化；基因倍增；生物复杂性；海七鳃鳗；基因表达调控网络

英文摘要： DNA methylation is an important epigenetics mechanism, which involves in the regulation of many biological processes. Its dysfunction can lead to a lot of human diseases such as cancer. Nowadays there are more than 20 sequenced eukaryotic methylomes. They significantly facilitated our understanding of the evolutionary pattern and their biological functions. However, we have little knowledge of methylation pattern and its function during the evolution from invertebrate to vertebrate, due to lacking of crucial species' DNA methylome. For example, as far as the evolution from mosaic to global pattern in DNA methylation is concerned, there is still a large controversy about whether its process is gradual or not. We also little know about the regulation relationship between DNA methylation and gene expression in the early stage of vertebrate evolution. To address such questions, we plan to use second-generation sequencing technology to sequence lamprey's heart and brain methylomes, their mRNA and miRNA transcriptomes, and Ciona intestinalis' heart and brain mRNA and miRNA transcriptomes. Combined with published data, our study will focus on how genome methylation pattern changes in the early stage of vertebrate evolution; how the change of methylation pattern affects gene expression; proposing and testing the epigene

英文关键词： DNA methylation；ene duplication；organism complexity；sea lamprey；gene regulatory network