酿酒酵母全基因组复制起始点的系统化分析及识别

DNA replication is one of the crucial steps in the cell cycle and cell development. Accurate duplication of the genome is required to ensure the faithful inheritance of genetic information from one cell generation to the next. DNA replication begins at a specific site, called origin of replication. Genome-wide systematic analysis and automatic recognition of replication origins in Saccharomyces cerevisiae can not only shed new light on the mechanism about replication and cell reproduction, but also have important theoretical significance in the regulation of replication capability and growth period of Saccharomyces cerevisiae. Here, we select Saccharomyces cerevisiae as model organism to analyze the sequence composition, structural properties, distribution characteristics and conservative features of replication origins etc. By using these features, we intent to develop an algorithm for recognizing replication origins in yeast genome automatically based on the Z-curve method. The experimental data related to the replication origins in Saccharomyces cerevisiae, such as high-throughput ARS screening with deep sequencing etc., will also be included for the improvement and optimization of the algorithm. We will establish a web-based platform to provide the experimental data as well as automatic recognition of replication origins in Saccharomyces cerevisiae. This work will provide new insight into the field of replication origins in yeast, which would be useful to reveal the mechanism of eukaryotic replication.

DNA复制是细胞周期和细胞发育的关键步骤之一，精确的DNA复制对维持生物遗传完整性具有至关重要的作用。DNA复制开始的特定位置被称为复制起始点。酵母是最简单的真核生物，对其复制起始点的研究，不仅有助于人们了解真核复制机制、揭示细胞增殖特性，而且对调节酵母复制功能、生长周期等方面有着非常重要的理论指导意义。本项目将酿酒酵母作为真核生物复制起始研究的模型，基于Z曲线理论，利用复制起始区的序列组成、结构特征、分布规律以及物种间保守特性等，开发出酿酒酵母复制起始点的自动化识别算法，并结合深度测序等实验数据来确保算法的准确性，对预测算法进行优化和改进。基于算法及实验所得数据，拟建立和发展酿酒酵母复制起始点自动识别软件和网上数据库服务系统。该项工作将有助于在全基因组水平上完善酿酒酵母复制起始点的相关研究，为进一步揭示真核生物复制机制奠定基础。

DNA复制是细胞增殖的重要事件，构成了生物遗传的基础。与原核生物相比，在真核基因组中DNA复制启动的复制起始点数量更多，在特定时间可被同时激活。在真核生物中，酿酒酵母复制起始点的研究最为透彻，其中自主复制序列是酵母复制起始点中的基本序列元素。对酵母复制起始点的识别有助于揭示真核DNA复制调控的相关机制。本项目通过群体基因组学分析，识别出了酿酒酵母种内超级保守序列、同源重组事件，并对复制起始点进行了全面的分析。基于复制起始区的序列特征以及群体基因组保守特性等，我们使用Z曲线方法开发出了酿酒酵母复制起始点的自动化识别算法，并最终建立和发展了酿酒酵母复制起始点自动识别软件Ori-Finder 3和网上数据库服务系统。在本项目资助下，项目负责人以第一作者/通讯作者身份在Nucleic Acids Research，Bioinformatics，Briefings in Bioinformatics等杂志发表论文18篇，作为客座主编出版英文电子书籍2本。该项工作有助于在全基因组水平上加深对酿酒酵母复制起始点的理解，并为酿酒酵母基因组设计奠定基础。