Phylogenomic approaches to understanding the phylogeny and early evolution of eukaryotes

在过去的几十年里，基因和基因组的计算分析表明，最熟悉的生物“王国”动物，真菌和植物只代表生命多样性的一个小角落。生物世界中最深刻的进化分歧是在细菌、微生物和“真核生物”之间。真核生物包括所有含细胞核的复杂细胞生物：动物、植物、真菌和大量同样重要的“王国”，其中大多数是微生物。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。许多新的微生物真核生物（原生生物）的超王国级群体（“超级群体”）不断被发现。这些谱系的位置和真核生物生命树中的基本划分仍然不清楚。因此，我们仍然缺乏所有真核细胞共同祖先的清晰图像，以及它最初是如何进化的。在五年的拟议研究中，学员，合作者和我将使用高通量DNA测序技术，比较基因组学方法和复杂的统计建模方法来解决这些关于生命之树的基本问题。首先，与Alastair Simpson的团队合作，我们将使用我们将从其基因组的表达部分获得的大量基因序列，将新发现的单细胞微生物置于真核生物生命树中。通过将这些新生物的基因序列数据与许多具有相同功能的基因序列进行比较，这些基因序列来自许多更好的特征谱系，包括简单的细胞生命（细菌和细菌），我们将描绘出真核生物生命树中最深的分支。然后，我们将描述新的原生生物的全基因组序列和其他研究不足的超级群体的代表。对这些数据进行复杂的计算分析将使我们能够推断出发生在超级群体共同祖先中的遗传创新，并有助于澄清所有真核生物共同祖先的遗传组成。通过这样做，我们将阐明生命进化史上的一些主要“转变”是如何以及何时在古代地球上发生的。最后，我们将投入相当大的努力，以改善实际的计算/统计进化方法，用于估计进化树的基因序列数据，并使这些新方法可在公开的软件工具。这将提高我们解析深层生命树的能力，但也将对其他基础和应用科学有用，包括追踪病毒传播和人口多样化等应用。这项研究的跨学科性质将为学员提供分子生物学，基因组学，生物信息学和统计学方面的重要可转移技能，以及批判性思维，指导，演示和技术写作。所有这些技能对生物或生物医学科学的职业都很有用。

In the last few decades, computational analysis of genes and genomes 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. Still, fundamental gaps remain in our understanding of early eukaryote evolution remain. Many new super-kingdom-level groups ('supergroups') of microbial eukaryotes (protists) continue to be discovered. The placement of these lineages and the fundamental divisions within the eukaryote tree of life remain unclear. As a result, we still lack a clear picture of the common ancestor of all eukaryotic cells and how it first evolved. Over the five years of the proposed research, trainees, collaborators and I will use high-throughput DNA sequencing technology, comparative genomics methods and sophisticated statistical modeling approaches to address these fundamental questions about the tree of life. First, in collaboration with Alastair Simpson's group, we will place newly discovered single-celled microbes in eukaryote tree of Life, using large numbers of gene sequences we will obtain from the expressed portions of their genomes. By comparing gene sequence data from these new organisms to gene sequences with the same functions from many better characterized lineages including simple cellular life (Bacteria and Archaea), we will delineate the deepest branches in the eukaryote tree of Life. We will then characterize the full genome sequences of novel protist organisms and representatives of other poorly-studied supergroups. Sophisticated computational analyses of these data will allow us to infer the genetic innovations occurred in the common ancestors of supergroups and help clarify the genetic makeup of the common ancestor of all eukaryotes. In so doing, we will shed light on 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 in improving the actual computational/statistical evolutionary methods used to estimate evolutionary trees from genetic sequence data and make these new methods available in publicly-available software tools. This will improve our abilities to resolve the deep tree of life, but will also be useful for other basic and applied science, including applications such as tracing viral spread and diversification in populations. The interdisciplinary nature of this research will furnish the trainees with important transferable skills in molecular biology, genomics, bioinformatics and statistics, as well as critical thinking, mentoring, presentation and technical writing. All of these skills are broadly useful for careers in the biological or biomedical sciences.