Evolution of the vesicle formation machinery

  • Author / Creator
    Schlacht, Alexander Douglas William
  • One of the features that distinguishes eukaryotes from prokaryotes is the membrane trafficking system. This system underpins much of the functionality of the eukaryotic cell, and is necessary for feeding, motility and communication. Analyses aimed at addressing the evolution of this system have revealed tremendous complexity in the Last Eukaryotic Common Ancestor, pointing to an even earlier origin. However, the events giving rise to this system and its subsequent diversification are poorly understood. Comparative genomic and phylogenetic analyses aimed at addressing the evolution of the membrane trafficking system have focused largely on the machinery of vesicle fusion. Here, I examine the evolution of machinery involved in vesicle formation. Comparative genomic and phylogenetic analyses were used to assess the conservation and evolution of protein families involved in the regulation of vesicle coat formation. ArfGAPs and ArfGEFs are regulatory proteins for the small GTPase Arf, a key regulator of vesicle coat formation. I found that five of ten previously identified ArfGAP subfamilies were present in the LECA, and I identify a previously unreported ArfGAP subfamily that is absent from humans and yeast. I also report that the LECA possessed three of the six described ArfGEF subfamilies. COPII is a heteromeric coat complex necessary for the transport of cargo from the endoplasmic reticulum to the Golgi apparatus. I found that all seven components were present in the LECA, five of which are ubiquitously conserved across eukaryotes. The other two are frequently missing. TSET is a newly identified adaptin-like coat complex with a likely role in endocytosis. I found that this complex is broadly distributed, indicating its presence in the LECA. However, it has been frequently lost from multiple eukaryotic lineages, including that giving rise to humans and fungi. Analysis of these gene families revealed multiple patterns of protein conservation, including ubiquitous and lineage-specific patterns, but also components with a “patchy” distribution that had previously been under appreciated. That some of these are missing from traditional cell biological systems such as humans and yeast, suggests the need to consider other eukaryotes as model organisms in order to fully comprehend the diversity of eukaryotic cell biology. Analysis of these components also revealed some of the earliest events that may have occurred during the evolution of the trafficking system, in addition to convergent roles of multiple coat complexes in membrane trafficking.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Turkewitz, Aaron (Department of Molecular Genetics, University of Chicago)
    • LaPointe, Paul (Department of Cell Biology)
    • Gallin, Warren (Department of Biological Sciences)
    • Melancon, Paul (Department of Cell Biology)