UC San Diego

One of the central ideas of Darwin's theory of descent with modification is that all life had a single origin, and all the various forms we see today are the result of variation and selection. 150 years later in the age of genomics we have realized there are three fundamentally distinct superkingdoms of life: the Archaea, Bacteria, and Eukaryotes. How did this these three groups evolve from one common ancestor? This dissertation attempts to answer that question with a variety of bioinformatics tools. The standard approach to this problem is to use mutations in protein sequence as a guide to construct phylogenetic trees. The failure of this approach has led many to argue there is no "tree of life". I argue against that strategy and conclusion by looking at the limitations of protein sequence data, and instead supplement it with other data sources. I argue that the rRNA trees which have been a standard of phylogeny for 30 years are misleading. They imply the root of the tree of life lies between the Archaea and the Bacteria. Instead of constructing trees, I have focused on creating timelines by differentiating between ancestral and derived taxa. The divergences in question occurred billions of years ago, so much of the signal present in sequence has degraded. Protein structure is more conserved than protein sequence on these time scales, so I use it as my tool of choice where ever possible. I argue the root of the tree of life is actually within the Gram-negative Bacteria and may have had a U-DNA genome. I have developed three polarizations that imply the Archaea are derived, and refuted all arguments that exclude the root from the Gram-negative Bacteria. One of these transitions led to the discovery of two novel proteasome homologs in Bacteria. It is not sufficient to argue the Archaea are derived from the Bacteria, one most provide a detailed explanation of how the most fundamental biological systems could all go through such a dramatic change to give rise to a novel superkingdom. I present a novel hypothesis that is a combination of selective pressure from antibiotic warfare, the right preadaptation in a Gram-positive bacterium, and relaxation of constraints from a viral endosymbiosis starting a chain of events that led to the birth of the Archaea