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Genomics and Phylogeny of Cytoskeletal Proteins: Tools and Analyses

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Genomics and Phylogeny of Cytoskeletal Proteins: Tools and Analyses Genomics and Phylogeny of Cytoskeletal Proteins: Tools and Analyses Dissertation zur Erlangung des mathematisch-naturwissenschaftlichen Doktorgrades „Doctor rerum naturalium“ der Georg-August-Universität vorgelegt von Björn Hammesfahr aus Ludwigsburg Göttingen 2012 Thesis Committee: PD Dr. Martin Kollmar (Referent) AG System-Biologie von Motorproteinen, Max-Planck-Institut für Biophysikalische Chemie Göttingen Prof. Dr. Burkhard Morgenstern (Co-Referent) Institut für Mikrobiologie und Genetik, Abteilung Bioinformatik, Georg-August-Universität Göttingen Dr. Dirk Fasshauer Associate Professor Department of Cell Biology and Morphology Faculty of Biology and Medicine University of Lausanne 1005 Lausanne Switzerland Tag der mündlichen Prüfung: 05.11.2012 Erklärung Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig angefertigt habe. Es wurden nur die in der Arbeit ausdrücklich benannten Quellen und Hilfsmittel benutzt. Wörtlich oder sinngemäß übernommenes Gedankengut habe ich als solches kenntlich gemacht. ______________________ _______________________ Datum, Ort Unterschrift 6 Erklärung Talks: March 2010 Alpbach Meeting, Myotin & Muscle and Many other Motors “CyMoBase – The Reference Database For Cyotskeletal And Motor Proteins” Poster presentations: February 2010 Biophysical Society 54th Annual Meeting, San Francisco (USA) “CyMoBase – The Reference Database For Cytoskeletal And Motor Proteins” March 2010 Alpbach Meeting, Myosin & Muscle and Many other Motors, Alpbach (Austria) “CyMoBase – The Reference Database For Cyotskeletal And Motor Proteins” October 2010 2nd Bio-IT World Europe, Hannover (Germany) “CyMoBase – The Reference Database For Cyotskeletal And Motor Proteins” July 2011 ISMB/ECCB, Vienna (Austria) “CyMoBase and diArk - Resources for cytoskeletal and motor protein sequence information and eukaryotic genome research” October 2011 3rd Bio-IT World Europe “diArk and CyMoBase – Resources for eukaryotic genome research, and cytoskeletal and motor protein sequence information” Table of contents 7 Table of contents Erklärung............................................................................................................... 5 Table of contents .................................................................................................. 7 1 Introduction ........................................................................................... 11 1.1 Bits of Life ............................................................................................................ 11 1.1.1 Genome ................................................................................................................. 11 1.1.2 Gene ...................................................................................................................... 14 1.2 Cytoskeletal Proteins ............................................................................................ 16 1.2.1 Cytoskeleton ......................................................................................................... 16 1.2.2 Microfilaments ...................................................................................................... 16 1.2.3 Intermediate filaments .......................................................................................... 17 1.2.4 Microtubules ......................................................................................................... 17 1.2.5 Motor proteins ....................................................................................................... 17 1.3 Protein Family Analyses ....................................................................................... 20 1.3.1 Why analysing a protein family? .......................................................................... 20 1.3.2 How analysing a protein family? .......................................................................... 20 1.3.3 Issues during a protein family analysis ................................................................. 21 1.3.4 Correctly predict and assemble proteins ............................................................... 22 1.3.5 Phylogenetic analysis ............................................................................................ 23 1.4 Databases and Web applications ........................................................................... 25 1.4.1 Database ................................................................................................................ 25 1.4.2 Web application .................................................................................................... 25 1.4.3 Development ......................................................................................................... 26 1.4.4 Deployment ........................................................................................................... 27 1.4.5 Set up a new database ........................................................................................... 27 1.4.6 NMR ..................................................................................................................... 28 2 Publications ........................................................................................... 30 2.1 Evolution of the eukaryotic dynactin complex, the activator of cytoplasmic dynein 30 2.1.1 Abstract ................................................................................................................. 30 2.1.2 Background ........................................................................................................... 31 2.1.3 Results ................................................................................................................... 33 2.1.4 Discussion ............................................................................................................. 49 2.1.5 Conclusions ........................................................................................................... 57 2.1.6 Methods ................................................................................................................ 57 2.1.7 Competing interests .............................................................................................. 59 2.1.8 Authors' contributions ........................................................................................... 59 2.1.9 Acknowledgements ............................................................................................... 60 8 Table of contents 2.1.10 Additional files ..................................................................................................... 60 2.1.10.1 Additional file 1 as ZIP ..................................................................................... 60 2.1.10.2 Additional file 2 as PDF .................................................................................... 60 2.1.10.3 Additional file 3 as PDF .................................................................................... 60 2.1.10.4 Additional file 4 as PDF .................................................................................... 60 2.1.10.5 Additional file 5 as PDF .................................................................................... 61 2.1.10.6 Additional file 6 as PDF .................................................................................... 61 2.1.10.7 Additional file 7 ................................................................................................ 61 2.1.10.8 Additional file 8 as PDF .................................................................................... 64 2.2 A holistic phylogeny of the coronin gene family reveals an ancient origin of the tandem-coronin, defines a new subfamily, and predicts protein function ........................... 65 2.2.1 Abstract ................................................................................................................. 65 2.2.2 Background ........................................................................................................... 66 2.2.3 Results ................................................................................................................... 67 2.2.4 Discussion ............................................................................................................. 82 2.2.5 Conclusions ........................................................................................................... 86 2.2.6 Methods ................................................................................................................ 86 2.2.7 Acknowledgements ............................................................................................... 88 2.2.8 Authors' contributions ........................................................................................... 88 2.2.9 Additional files ..................................................................................................... 88 2.2.9.1 Additional file 1 – Sequence alignment of the coronins ................................... 88 2.2.9.2 Additional file 2 – MrBayes tree of the coronin family .................................... 88 2.2.9.3 Additional file 3 – RAxML tree of the coronin family ..................................... 89 2.2.9.4 Additional file 4 – Coronin repertoire of all eukaryotes analyzed .................... 89 2.2.9.5 Additional file 5 – Conserved residues in the coronin domain ......................... 89 2.3 diArk 2.0 provides detailed analyses of the ever increasing eukaryotic genome sequencing data...................................................................................................................
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