Grant: Discovery Grants Program - Individual

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.