EAPSI: Exploring 3-D DNA Organization and Evolution in a Microbial Eukaryote

在过去的几十年里，我们对DNA在细胞核中的组织方式的理解是从一个麻袋演变而来的。充满染色体的高度有序的结构。尽管越来越多的证据表明基因组在细胞核中的组织方式是保守的和适应性的，但很少有研究从三维角度探索基因组进化及其组织的关系。这在一定程度上是由于目前人们对基因组进化的看法，基因组序列被视为长线性分子，而不是实际存在于真核细胞内的高度折叠的染色体。与中央研究院的姚梦超博士合作，该项目将与托克夫里亚sp.合作。(一种不寻常的微生物真核生物？基因大小？染色体和复杂的生命周期)作为研究有机体来探索进化的模式，以及进化是如何反映在其核结构中的。目前，除了其序列之外探索真核生物基因组进化的研究很少。通过使用定量聚合酶链式反应和荧光原位杂交等分子工具，该项目将能够估计不同大小基因的实际丰度。染色体、它们的相对表达以及它们的位置。将托克夫里亚的这些物理特性与生物信息学方法结合起来探索分子进化模式，如成对距离和密码子偏向，将为强有力的比较研究提供基础。以前在微生物真核生物方面的工作已经帮助证明了一些普遍的？核结构中的模式，例如将DNA组织到DNA贫乏走廊周围的DNA富集区。进一步与不同的生物体，如托克夫里亚属进行合作。将提供有关分子进化和进化力量如何参与三维基因组的非随机组织之间的关系的详细信息。该奖项由东亚和太平洋暑期学院项目资助一名美国研究生的暑期研究，由美国国家科学基金会和台湾科技部联合资助。

Over the last few decades, our understanding of how DNA is organized in the nucleus has evolved from a ?sack? full of chromosomes to a highly ordered structure. Despite the growing evidence for conserved and adaptive patterns in how the genome is organized in the nucleus, there are few studies exploring the relationship of genome evolution and its organization in 3-dimensions. This is partly due to the way that genome evolution is currently perceived, where genomic sequences are treated as long linear molecules rather than the highly folded chromosomes that actually exist inside the eukaryotic cell. In collaboration with Dr. Meng-Chao Yao, at Academia Sinica, this project will work with Tokophrya sp. (an unusual microbial eukaryote with ?gene-sized? chromosomes and a complex life cycle) as the study organism to explore patterns of evolution and how evolution is reflected in its nuclear architecture.Currently, there are few studies exploring the evolution of the eukaryotic genome beyond its sequence. Through the use of molecular tools such as qPCR and fluorescence in situ hybridization, the project will be able to estimate the actual abundance of different ?gene-sized? chromosomes, their relative expression, and their position as well. Coupling these physical properties of Tokophrya with bioinformatic approaches to explore patterns of molecular evolution such as pairwise distances and codon bias will provide the basis for a strong comparative study. Previous work in microbial eukaryotes has helped to demonstrate some ?universal? patterns in nuclear architecture, such as the organization of DNA into DNA rich regions surrounding DNA poor corridors. Further work with divergent organisms such as Tokophrya sp. will provide intimate details about relationship between molecular evolution and how evolutionary forces participate in the non-random organization of the 3-dimensional genome. This award under the East Asia and Pacific Summer Institutes program supports summer research by a U.S. graduate student and is jointly funded by NSF and the Ministry of Science and Technology of Taiwan.