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Molecular Evolution of Hominoid Primates: Phylogeny and Regulation Ranajit Das

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Duquesne University Duquesne Scholarship Collection Electronic Theses and Dissertations Fall 2014 Molecular Evolution of Hominoid Primates: Phylogeny and Regulation Ranajit Das Follow this and additional works at: https://dsc.duq.edu/etd Recommended Citation Das, R. (2014). Molecular Evolution of Hominoid Primates: Phylogeny and Regulation (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/461 This Immediate Access is brought to you for free and open access by Duquesne Scholarship Collection. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Duquesne Scholarship Collection. For more information, please contact [email protected]. MOLECULAR EVOLUTION OF HOMINOID PRIMATES: PHYLOGENY AND REGULATION A Dissertation Submitted to the Bayer School of Natural and Environmental Sciences Duquesne University In partial fulfillment of the requirements for the degree of Doctor of Philosophy By Ranajit Das December 2014 Copyright by Ranajit Das 2014 MOLECULAR EVOLUTION OF HOMINOID PRIMATES: PHYLOGENY AND REGULATION By RANAJIT DAS 23rd June 2014 ________________________________ ________________________________ Dr. Michael Jensen-Seaman Dr. Brady Porter Associate Professor of Biological Associate Professor of Biological Sciences Sciences (Committee Chair) (Committee Member) ________________________________ ________________________________ Dr. David Lampe Dr. Nathan Clark Associate Professor of Biological Assistant Professor of Computational and Sciences Systems Biology, University of Pittsburgh (Committee Member) (Committee Member) ________________________________ ________________________________ Dr. Philip Reeder Dr. Joseph McCormick Dean, Bayer School of Natural and Chair, Biological Sciences Environmental Sciences Associate Professor of Biological Sciences iii ABSTRACT MOLECULAR EVOLUTION OF HOMINOID PRIMATES: PHYLOGENY AND REGULATION By Ranajit Das December 2014 Dissertation supervised by Dr. Michael Jensen-Seaman The complete mitochondrial genome of one eastern gorilla was sequenced to provide the most accurate date for the mitochondrial divergence of gorillas. The most recent common ancestor of eastern lowland and western lowland gorillas existed about 1.9 million years ago, slightly more recent than that of chimpanzee and bonobo. This confirms that the eastern and western gorillas show species level genetic divergence. Hominoid mating systems differ tremendously. The level of sperm competition varies according to the mating system, which presumably imposes unique selective pressures on the seminal proteins of each species. Cartilage acidic protein 1 (CRTAC1) was identified in our lab as the protein with the largest difference in abundance between human and chimpanzee semen, being found at 142-fold higher in chimpanzee. The coding region of CRTAC1 is extremely conserved with signature of strong purifying selection. Paradoxically, the CRTAC1 ‘promoter’ from human drives transcription iv significantly greater than chimpanzee, with or without androgen stimulation. Analyzing H3K27Ac data, a ~2.2kb region was identified as a possible additional cis-regulatory element. The cis-regulatory region behaved like a silencer and aided in strong transcriptional repression in humans. Although its underlying basis remains elusive, it can be speculated that the differential expression of CRTAC1 between human and chimpanzee seminal plasma results from tissue specific over/under expression of this gene. The evolutionary history of micro RNAs (miRNAs) within hominoids have remained understudied. The overall goal of this project was to identify the uniquely gained and lost miRNAs and their targets within hominoids. I found 14 miRNAs uniquely gained in humans, the targets of which are associated with brain-associated functions. Older miRNAs were found to be more conserved compared to the newer miRNAs gained within the last 15 million years. v ACKNOWLEDGEMENT There are a number of people I want to thank for their support during my graduate career at Duquesne University and for making my journey here a memorable one. First, I want to thank my dissertation advisor, Dr. Michael Jensen-Seaman for his support and advice over the years. He has been a terrific mentor and his guidance has been critical for not for the successful completion of my work in his lab but will always be an important guide in my scientific journey ahead. I want to thank my dissertation committee, Dr. Brady Porter, Dr. David Lampe and Dr. Nathan Clark for their support and valuable advice to my dissertation research and for helping to improve my scientific training at Duquesne University. I want to thank all the past and present members of the Seaman lab, Dr. Sarah Craig, Scott Hergenrother, Amanda Colvin, Jennifer Vill, Alicia Martinez, and Lindsay Kokoska for their help over the years. In addition, I want to thank the Selcer, Auron, Castric, McCormick, and Lampe labs at Biological Sciences, Duquesne University for sharing equipment and reagents over the years. Further I would like to thank the Duquesne University Core Sequencing Facility and staff members at the Biological Sciences Main Office for their help and support during my graduate career at Duquesne University. I want to thank all my family especially my parents, Debjani Das and Laxmikanta Das for their love and unconditional support through all my pursuits. They have not only always been there for me but have always encouraged me to dream bigger and strive harder towards my life goals. Today would not have been possible without their love and blessings. vi Finally I want to thank my wife, Dr. Priyanka Upadhyai for her friendship, love, and support and for being my biggest strength over the years. More so, I feel fortunate that we share not only our lives but also a passion for science that has helped surmount many an obstacle over the years. vii TABLE OF CONTENTS ABSTRACT ...................................................................................................................... iv ACKNOWLEDGEMENT ............................................................................................... vi TABLE OF CONTENTS .............................................................................................. viii LIST OF TABLES ......................................................................................................... xiii LIST OF FIGURES ........................................................................................................ xv Chapter 1: Introduction ................................................................................................... 1 1.1 Introduction to Primates ........................................................................................ 1 1.1.1 Primates as mammals ..........................................................................................1 1.1.2 Primate classification ..........................................................................................2 1.1.3 Primate habit and habitat.....................................................................................4 1.2 Sexual selection........................................................................................................ 5 1.3 Eukaryotic gene regulation .................................................................................. 10 References .................................................................................................................... 15 Chapter 2: Evolutionary history of gorillas inferred from complete mitochondrial genome sequences............................................................................................................ 21 2.1 Introduction ........................................................................................................... 21 2.1.1 Brief introduction to gorilla phylogeography ...................................................21 2.1.2 Bayesian inference of phylogeny ......................................................................23 2.1.2.1 Introduction to Bayesian statistics ............................................................ 24 2.1.2.2 Bayesian phylogeny vs. other phylogenies: pros and cons ....................... 25 2.1.2.3 Technical details of Bayesian phylogeny ................................................. 26 2.1.3 Introduction to mitochondrial genome in respect to phylogenetics ..................28 2.2 Methods .................................................................................................................. 30 2.2.1 DNA sequencing ...............................................................................................31 2.2.2 Primate mtDNA Sequence Alignments ............................................................31 2.2.3 Protein coding genes, tRNA and rRNA analysis ..............................................32 2.3.4 Phylogenetic analysis ........................................................................................34 2.3.4.1 Bayesian approach .................................................................................... 34 2.3.4.2 Maximum Likelihood approach ................................................................ 36 2.3 Results .................................................................................................................... 36 2.3.1 DNA sequencing ...............................................................................................36 2.3.2 Dating species splits using mtDNA ..................................................................37
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