Elucidation of the machinery of biodiversity on the basis of evolutionary genetics

在这个研究项目中，我们试图从进化遗传学的角度来解释自35亿年前以来生物有机体通过进化获得的生物多样性。目前，人类等各种物种的大量完整基因组序列已经可用，数百个基因组测序项目被认为正在进行中。因此，这些基因组给了我们一个启动生物多样性分析项目的机会。在第一个学年，我们检测了真核生物基因组中的重复区域，例如人类。为了提高检测的准确性，我们开发了一种新的统计方法来寻找有意义的重复区域。因此，我们成功地在人类、酵母和蠕虫中分别鉴定出74个重复区域、59个重复区域和197个重复区域。我们为这些结果建立了一个数据库，这样任何人都可以通过互联网使用图形用户界面来访问我们的数据。在第二个学年，为了详细分析人类MHC区域，新确定了该区域的一个大DNA序列(~400kb)。结果，我们发现了大的基因组复制，并重建了复制的进化过程。此外，在非编码区发现了高度的核苷酸多样性，这意味着这些区域可能已经发生了搭便车效应。接下来，我们将研究扩展到微生物，并可能揭示出，通常情况下，细菌基因组结构即使在被认为是重要功能单位的操纵子中也是相当不稳定的。此外，我们还开发了一种新的方法来检测GC含量变化的进化方向，这导致了基因组的高度多样性。

In this research project, from the viewpoint of evolutionary genetics we attempted to elucidate biodiversity that living organisms have acquired through evolution since the beginning of 3.5 billion years ago. Currently, a lot of complete genome sequences from a variety of species such as human are available, and hundreds of genome-sequencing projects are thought to be underway. Thus, these genomes gave us an opportunity to initiate the project of biodiversity analysis.In the first academic year we conducted detection of duplicated regions in eukaryotic genomes such as human. In order to improve the accuracy of the detection, we developed a new statistical method of finding significant duplicated regions. Consequently, we successfully identified 74 duplicated regions in human, 59 in yeast, and 197 in worm. We constructed a database for these results, so that anyone can access our data through Internet by using a graphical user interface. The times of duplication events were estimated so as to study what the duplication affect to evolution.In the second academic year, in order to analyze the MHC region of human in detail, a large DNA sequence (〜400 kb) in the region was newly determined. As a result, we found large genome duplication, and reconstructed the evolutionary process of the duplication. Moreover, high nucleotide diversity was found in non-coding regions, implying that hitchhiking effects might have occurred in the regions. Next, we extended our study to microbes, and could reveal that in general bacterial genome structures are quite unstable even in operons that are believed to be functionally important units. In addition, we developed a new method for the detection of evolutionary direction of GC-content change, which leads to high diversity of genomes.