University of Central Florida STARS Electronic Theses and Dissertations, 2004-2019 2007 Modeling And Partitioning The Nucleotide Evolutionary Process For Phylogenetic And Comparative Genomic Inference Todd Castoe University of Central Florida Part of the Biology Commons Find similar works at: https://stars.library.ucf.edu/etd University of Central Florida Libraries http://library.ucf.edu This Doctoral Dissertation (Open Access) is brought to you for free and open access by STARS. It has been accepted for inclusion in Electronic Theses and Dissertations, 2004-2019 by an authorized administrator of STARS. For more information, please contact [email protected]. STARS Citation Castoe, Todd, "Modeling And Partitioning The Nucleotide Evolutionary Process For Phylogenetic And Comparative Genomic Inference" (2007). Electronic Theses and Dissertations, 2004-2019. 3111. https://stars.library.ucf.edu/etd/3111 MODELING AND PARTITIONING THE NUCLEOTIDE EVOLUTIONARY PROCESS FOR PHYLOGENETIC AND COMPARATIVE GENOMIC INFERENCE by TODD A. CASTOE B.S. SUNY – College of Environmental Science and Forestry, 1999 M.S. The University of Texas at Arlington, 2001 A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomolecular Sciences in the Burnett College of Biomedical Sciences at the University of Central Florida Orlando, Florida Spring Term 2007 Major Professor: Christopher L. Parkinson © 2007 Todd A. Castoe ii ABSTRACT The transformation of genomic data into functionally relevant information about the composition of biological systems hinges critically on the field of computational genome biology, at the core of which lies comparative genomics. The aim of comparative genomics is to extract meaningful functional information from the differences and similarities observed across genomes of different organisms. We develop and test a novel framework for applying complex models of nucleotide evolution to solve phylogenetic and comparative genomic problems, and demonstrate that these techniques are crucial for accurate comparative evolutionary inferences. Additionally, we conduct an exploratory study using vertebrate mitochondrial genomes as a model to identify the reciprocal influences that genome structure, nucleotide evolution, and multi-level molecular function may have on one another. Collectively this work represents a significant and novel contribution to accurately modeling and characterizing patterns of nucleotide evolution, a contribution that enables the enhanced detection of patterns of genealogical relationships, selection, and function in comparative genomic datasets. Our work with entire mitochondrial genomes highlights a coordinated evolutionary shift that simultaneously altered genome architecture, replication, nucleotide evolution and molecular function (of proteins, RNAs, and the genome itself). Current research in computational biology, including the advances included in this dissertation, continue to close the gap that impedes the transformation of genomic data into powerful tools for the analysis and understanding of biological systems function. iii This dissertation is dedicated to my wife, my family, my close friends, and to the memory of Kenneth and Mary Van Norstrand. Their love, support, respect, encouragement, and genuine depth of character are the only reasons that this particularly extraordinary process has been possible. My appreciation for their roles in my life cannot be overstated, and this dissertation stands as one humble anecdotal testament of the strength of their conviction and virtue. Despite the copyright on the preceding page, the credit for this work belongs to them. iv ACKNOWLEDGMENTS My advisor, Christopher Parkinson, has somehow found the patience to endure many years of dealing with all of my personality quirks, the significance of which is obvious and enormous for anyone who knows me well. He has always supported my independence and facilitated my growth as a biologist eager to choose his own course. He has done his best to encourage and enable my success and scientific development, and we have shared many fun experiences together, and I sincerely thank him for his guidance, patience, and friendship. The UCF Department of Biology has supported my work in many ways, including both financial and moral support. I was supported by a fellowship from the UCF Graduate School, and indirectly through support received by Chris Parkinson in the form of his startup funds from the UCF Biology Department, and from his National Science Foundation grant (DEB–0416000). My committee, including Laurie Von Kalm, Henry Daniel, and Jack Ballantyne has consistently provided a very important platform of encouragement and support throughout the entire process and I sincerely thank them for their positive role throughout my dissertation work. Even beyond academic relationships, the personal relationships that I have had the pleasure of sharing with both Laurie and Henry have been particularly important to my keeping focused and enthusiastic, and for this I thank them both. I would like to thank David Pollock and members of his lab (especially Zhijie Jiang and Wanjun Gu) for their collaborative support on mitochondrial genome projects. Rather than competing with one another, collectively we have enjoyed a rewarding collaborative experience that has resulted in many positive things being accomplished. Their help and encouragement, v both on specific projects and in general, have played key roles in the success of many of the mitochondrial genome-based projects included here and to come. Zhijie Jiang also has delivered a number of important favors and I sincerely appreciate his patience, understanding, and much- needed help. Throughout my time at UCF I have been particularly fortunate to have overlapped with a large number of truly exceptional people, both in the lab, and in the program. These close friends have tremendously enriched my experience here and their constant support and friendship have played key roles in my enjoyment and success. A number of great people in the lab have had the misfortune of co inhabiting 425 (and earlier labs) with me, all of which played major roles in my development as a scientist, and also acted as important cheerleaders providing constant encouragement over the years, one cup of coffee at a time. Josh Reece always talked me into a camping trip when I needed a break. Jack Degner always talked me into a beer when he knew I needed one, and our mutual love for Tom Waits songs effectively erased thoughts of scientific failures of the preceding days, or at least erased previous thoughts altogether. Matt (dirty red) Herron was around back in the good old days when we thought 1 million MCMC generations deserved a Nature paper; wouldn’t that be nice if things stayed that way eh Matt? Håkon (makemecupacoffee) Kalkvik provided many much needed coffee breaks, sober safe rides home, and lots of great chocolate to fuel my scientific fires. Jenna, the little sister of the lab, always provided some much needed sarcasm and a good laugh to reduce the ambient tension in the air. Allyson Modra – finally a coffee lover in the lab – actually helped me take less coffee breaks and I probably owe her for getting out of here on time. Juan (el gordo) Daza has been a great friend, vi drinking buddy, fellow naïve biogeographer, and snake lover, and together we have shared many good times and avoided some paramilitary. I owe a huge debt of gratitude to Robert Ruggiero, my long-time roommate and old friend. A majority of my academic career has been shared with Rob and it is often difficult to disassociate my path from him and his impact on it. Above all, I need to thank him for his relentless support, solid advice, and for making this otherwise tedious and frustrating process an exciting and enriching experience. I am a better scientist because of my years of interaction and friendship with Rob. Sam and Erin Fox, our close friends and confidants, positively distracted us in many memorable and enjoyable ways, including introducing us to many new forms of adventure: surfing, clothing optional rooftop bars, and a previously underrated brand of cheap whiskey - Dickel. We definitely miss all these characters and look forward to meeting them soon somewhere above 10,000 ft. in the Rockies, one day soon with Ph.Ds of their own. My cohorts in the Biomolecular Sciences Ph.D. program happened to be an amazing group of people who made these 5 years particularly special. Even if we don’t see each other as much as we used to, my relationship with them is as close as it ever was, and this way it will remain. My closest confidant and buddy, George Kryazis, has remained a steadfast unflinching bedrock of support, advice, and encouragement throughout this process, and I really hope that he gets rich someday (and shares) so we both don’t have to waste beautiful expensive bottles of scotch complaining about science any longer. Claudia, whom I essentially look to as a big sister, really set the bar pretty high around these parts (gee thanks) and proved to us all upfront that finishing a PhD was possible. Max Chen, Mangala Soundarapandian, and Paul Cohill have comprised a excellent group of study partners, commiseraters, entertainers, and loyal friends vii throughout the last five years and I will surely miss their faces and personalities, hopefully not for too long. In addition to those above, many others shared great times in Orlando, predominantly spent in the dingy booths of a lesser-known hot-spot named Underground Bluz or at our place – the home of the Cosmopolitan. With Walter Sotero, Pierre Decayette, Amit Dhingra, and Tanya Vargas, we spent many fun and memorable evenings together, as these folks rounded out a makeshift home-away-from home and novel extended family. Make new friends but keep the old, the first are silver, the latter gold. There is surely some truth to this, and many old friends from the beginning of my graduate career in Texas have remained close friends, collaborators, and invaluable scientific resources. Eric and Karin Smith have remained very close friends for many years, and over many miles.