Phylogenomic approaches to inferring ancient relationships among eukaryotes

在过去的几十年里，对基因和基因组数据的计算分析表明，最熟悉的生物王国——动物、真菌和植物——只代表了生命多样性的一个很小的角落。生物世界中最深的进化分歧是在细菌、古生菌和真核生物之间。真核生物包括所有含核的复杂细胞生物：动物、植物、真菌和大量同样重要的主要由微生物组成的生物王国。我们现在知道真核生物基本上是嵌合的：15亿多年前，一个与古细菌有关的细胞与一个细菌细胞共生，而这个细菌细胞最终变成了产生能量的细胞器，即线粒体。尽管如此，我们对早期真核生物进化的理解仍然存在根本性的差距，例如，这种细菌共生体是具有复杂代谢的自由生活形式，还是已经是一种简化的寄生虫，以及真核生物是如何首先分化成今天地球上的几十个王国的。***在五年的研究中，我和12名学员将使用高通量DNA测序技术和基因组学方法，并开发复杂的统计建模方法，解决三个基本的进化问题。首先，我们将通过表征34种可能与线粒体密切相关的活细菌的基因组来研究线粒体的起源。这将使我们能够推断出原始共生体的特性，澄清导致它们整合为真核细胞不可或缺的部分的选择力。其次，我们将利用从单细胞真核生物基因组表达部分获得的数据，阐明真核生物生命树中最基本的划分。我们将研究的物种代表了特征非常差的王国，目前正在被我们的合作者分离和表征。通过将这些新生物的数据与许多更有特征的谱系的数据进行比较，我们将描绘出真核生物生命树中最深的分支。这些数据也用于我们的第三个问题，即确定真核生物树中哪个分支是最早的。通过这样做，我们将阐明生命进化史上的一些主要“转变”是如何以及何时发生在古代地球上的。最后，我们将投入相当大的努力来改进用于进行此类分析的实际计算/统计方法。这将改进我们的研究，但对其他基础科学和应用科学也普遍有用。******这项研究的跨学科性质将为受训者提供分子生物学、基因组学、生物信息学和统计学方面的关键科学技能，以及批判性思维、演讲和技术写作。所有这些技能在生物或生物医学科学的职业生涯中都很有用。********

In the last few decades, computational analysis of genes and genomics data have shown that the most familiar biological kingdoms' - animals, fungi and plants - represent only a tiny corner of the diversity of Life. The deepest evolutionary divergences in the living world are between Bacteria, Archaea and Eukaryotes'. Eukaryotes includes all the nucleus-containing complex-celled organisms: animals, plants, fungi and a huge number of equally important kingdoms' that are mostly microbes. We now know that eukaryotes are fundamentally chimeric: More than 1.5 billion years ago, a cell related to Archaea took up a bacterial cell as a symbiont, and this second cell eventually became energy-producing organelles known as mitochondria. Still, fundamental gaps remain in our understanding of early eukaryote evolution, for example, whether this bacterial symbiont was a free-living form with a complex metabolism, or already a simplified parasite, and how eukaryotes first diversified into the dozens of kingdoms' on Earth today.***Over the five years of the proposed research, 12 trainees and I will use high-throughput DNA sequencing technology and genomics methods, and develop sophisticated statistical modeling methods, to address three fundamental evolutionary questions. First, we will examine the origin of mitochondria by characterizing the genomes of ~34 living bacteria that are likely to be closely related to mitochondria. This will allow us to infer the properties of the original symbionts, clarifying the selective forces that led to their integration as indispensible parts of the eukaryotic cells. Second, we will clarify the most fundamental divisions within the eukaryote tree of Life, using data we will obtain from the expressed portions of the genomes of single-celled eukaryotes. The species we will examine represent very poorly characterised kingdoms', and are currently being isolated and characterized by our collaborators. By comparing data from these new organisms to data from many better characterized lineages, we will delineate the deepest branches in the eukaryote tree of Life. These data are also used for our third question, establishing which division in the eukaryotic tree was the earliest. In so doing, we will clarify how and when some of the major 'transitions' in evolutionary history of Life took place on the ancient Earth. Finally, we will invest considerable effort to improve the actual computational/statistical methods used to conduct such analyses. This will improve our research, but will be generally useful for other basic and applied science.******The interdisciplinary nature of this research will furnish the trainees with critical scientific skills in molecular biology, genomics, bioinformatics and statistics, as well as critical thinking, presentation and technical writing. All of these skills are broadly useful for careers in the biological or biomedical sciences.********