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Evolutionary Analysis of the CAP Superfamily of Proteins Using Amino Acid Sequences

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Evolutionary Analysis of the CAP Superfamily of Proteins Using Amino Acid Sequences Evolutionary Analysis of the CAP Superfamily of Proteins using Amino Acid Sequences and Splice Sites by Anup Abraham A Thesis Presented in Partial Fulfillment of the Requirements for the Degree Master of Science Approved April 2016 by the Graduate Supervisory Committee: Douglas E. Chandler, Chair Kenneth H. Buetow Robert W. Roberson ARIZONA STATE UNIVERSITY May 2016 ABSTRACT Here I document the breadth of the CAP (Cysteine-RIch Secretory Proteins (CRISP), Antigen 5 (Ag5), and the Pathogenesis-Related 1 (PR)) protein superfamily and trace some of the major events in the evolution of this family with particular focus on vertebrate CRISP proteins. Specifically, I sought to study the origin of these CAP subfamilies using both amino acid sequence data and gene structure data, more precisely the positions of exon/intron borders within their genes. Counter to current scientific understanding, I find that the wide variety of CAP subfamilies present in mammals, where they were originally discovered and characterized, have distinct homologues in the invertebrate phyla contrary to the common assumption that these are vertebrate protein subfamilies. In addition, I document the fact that primitive eukaryotic CAP genes contained only one exon, likely inherited from prokaryotic SCP-domain containing genes which were, by nature, free of introns. As evolution progressed, an increasing number of introns were inserted into CAP genes, reaching 2 to 5 in the invertebrate world, and 5 to 15 in the vertebrate world. Lastly, phylogenetic relationships between these proteins appear to be traceable not only by amino acid sequence homology but also by preservation of exon number and exon borders within their genes. i TABLE OF CONTENTS Page LIST OF FIGURES ........................................................................................................... iv LIST OF APPENDIX FIGURES....................................................................................... vi LIST OF SUPPLEMENTAL DATA TABLES ................................................................ vii CHAPTER 1 INTRODUCTION ................................................................................................... 1 2 IN-DEPTH ANALYSIS OF CAP SUPERFAMILY PROTEINS .......................... 5 The CAP Superfamily Proteins: Domains, Sequences and Structural Relationships . 5 Bacterial, Plant, and Fungal SCP/PR Proteins ............................................................ 8 CAP Proteins of Insects: the Venom Allergen Subfamily ........................................ 14 The Cysteine-RIch Secretory Protein (CRISP) Subfamily ....................................... 17 Truncated CRISP (Allurin) ........................................................................................33 The LCCL Domain-containing Subfamily ................................................................ 33 The GLIPR/GLIPR-like Subfamily .......................................................................... 34 The GAPR Subfamily ............................................................................................... 36 The Peptidase Inhibitor Subfamily ............................................................................ 38 3 EVOLUTION OF CAP SUPERFAMILY GENE STRUCTURE ......................... 40 Evolution of CAP Superfamily Gene Structure ........................................................ 40 Conservation of Exon Borders within CAP Subfamily Genes ................................. 43 Physical Clustering of CAP Subfamily Genes in the Genome ................................. 57 The Origins of CAP Subfamilies with Emphasis on the Evolution of CRISP Genes58 4 EVOLUTION OF CRISP GENE STRUCTURE .................................................. 66 ii CHAPTER Page Evolution of the CAP/PR Domain ............................................................................ 66 Addition of the Hinge Domain .................................................................................. 69 Addition of the ICR Domain ..................................................................................... 71 5 CONCLUSION ...................................................................................................... 75 BIBLIOGRAPHY .............................................................................................................81 APPENDIX A FIGURES ..............................................................................................................91 B TABLES ..............................................................................................................142 iii LIST OF FIGURES Figure Page 1. Subfamilies of the CAP Superfamily ...................................................................... 4 2. Domain Structure of CAP Proteins ......................................................................... 7 3. ClustalW Amino Acid Alignment of the CAP/PR Domain in Bacterial SCP Proteins ................................................................................................................... 9 4. ClustalW Amino Acid Alignment of the CAP/PR Domain in Plant Pathogenesis- Related Proteins .................................................................................................... 11 5. ClustalW Amino Acid Alignment of the CAP/PR Domain in Fungal CAP Superfamily Proteins ............................................................................................. 13 6. Tertiary Structure of the Tomato P14a Pathogenesis-Related Protein ................. 14 7. ClustalW Amino Acid Alignment of Insect Antigen-Related Proteins ................ 16 8. ClustalW Amino Acid Alignment of Vertebrate CRISP2 and CRISP2-like Proteins ................................................................................................................. 19 9. Domain Organization and Tertiary Structure of a Full Length CRISP Protein: Venom CRISP from the Chinese Cobra ............................................................... 24 10. ClustalW Amino Acid Alignment and Secondary Structure of Selected CRISP Proteins ................................................................................................................. 25 11. ClustalW Amino Acid Alignment of Invertebrate CRISP2-like Proteins ............ 27 12. Global Genome Relatedness between Selected Organisms in This Study ........... 42 13. Genomic Exon Border Structure in Selected Vertebrate CRISP2 and CRISP2-like Genes..................................................................................................................... 44 iv Figure ....................................................................................................................... Page 14. ClustalW Amino Acid Alignment for Exon Borders in Selected CRISP and CRISP-like Genes ................................................................................................. 46 15. Genomic Exon Border Structure in Selected Invertebrate CRISP and CRISP-like Amino Acid Sequences ......................................................................................... 48 16. Evolution of CAP Proteins is accompanied by an Increase of Exons Representing the CAP/PR Domain ............................................................................................. 49 17. Phylogenetic Relationships of CAP Superfamily Proteins in the X. tropicalis (Western Clawed Frog) Genome .......................................................................... 53 18. Genomic Exon Border Structure in CAP Superfamily Proteins in the X. tropicalis (Western Clawed Frog) Genome .......................................................................... 54 19. Phylogenetic Relationships Of All CAP Superfamily Proteins in the Homo sapiens (Human) Genome ..................................................................................... 55 20. Genomic Exon Border Structure In All CAP Superfamily Proteins in the Homo sapiens (Human) Genome ..................................................................................... 56 21. Genomic Clustering Data of CAP Superfamily Genes in Representative Genomes ............................................................................................................................... 62 22. Evolution of Multi-Domain CAP Superfamily Proteins ....................................... 64 23. Evolution of CRISP Proteins is Accompanied by Placement of Introns and Cysteines at Specific Positions ............................................................................. 68 24. The ICR Domain is Related to Potassium Channel Toxins .................................. 71 25. Point of Origin for Various CAP Superfamily Proteins ....................................... 73 26. Point of Origin for Various CAP Superfamily Proteins ...................................... 78 v APPENDIX A FIGURES Figure Page 1. A. Inventory of CAP-related Proteins in Selected Species ....................................92 B. Phylogenetic Tree vs Number of CAP Protein in Genome ...............................96 2. ClustalW Amino Acid Alignment and Color-Coded Mapping of Exons for Selected Sequences ................................................................................................97 3. ClustalW Amino Acid Alignment and Color-Coded Mapping of Exons for Selected Invertebrate CAP Protein Sequences ....................................................104 4. ClustalW Amino Acid Alignment and Color-Coded Mapping of Exons for CAP Superfamily Genes in X. tropicalis Genome .......................................................108
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