Phylogenomic approaches to understanding the phylogeny and early evolution of eukaryotes

在过去的几十年里，对基因和基因组的计算分析表明，最常见的生物“王国”动物、真菌和植物只代表生命多样性的一小部分。生物世界中最深的进化分歧存在于细菌、古生菌和“真核生物”之间。真核生物包括所有含有核的复杂细胞有机体：动物、植物、真菌和大量同样重要的主要是微生物的“王国”。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。许多新的超王国级别的微生物真核生物(原生生物)群(‘超群’)继续被发现。这些血统在真核生物生命树中的位置和基本划分仍然不清楚。因此，我们仍然缺乏关于所有真核细胞的共同祖先以及它最初是如何进化的清晰图景。在拟议的五年研究中，受训者、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树的基本问题。首先，我们将与阿拉斯泰尔·辛普森的团队合作，利用我们将从它们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放入真核生物的生命树中。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，包括简单的细胞生命(细菌和古生菌)，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和其他研究较少的超群的代表的全基因组序列。对这些数据的复杂计算分析将使我们能够推断超群的共同祖先中发生的基因创新，并有助于澄清所有真核生物共同祖先的基因构成。通过这样做，我们将阐明生命进化史上的一些重大“转变”是如何以及何时在古老的地球上发生的。最后，我们将投入相当大的努力来改进用于从遗传序列数据估计进化树的实际计算/统计进化方法，并使这些新方法在公开可用的软件工具中可用。这将提高我们解析生命之树深处的能力，但也将对其他基础科学和应用科学有用，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重要可转让技能，以及批判性思维、指导、陈述和技术写作。所有这些技能对生物或生物医学科学的职业生涯都是非常有用的。

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.