Mobile genetic elements : mechanisms of microbial evolution and reservoirs of genome engineering tools
Abstract/Contents
- Abstract
- Mobile genetic elements (MGEs) are genetic material that can mobilize and move either within a single organism's genome, or between the genomes of different organisms. An integrative mobile genetic element is one that can merge its genetic material with other genetic molecules to form a single genetic molecule, either DNA or RNA. Thanks to the work of pioneering scientists such as Nobel Laureate Barbara McClintock, our knowledge of how MGEs work and how they influence evolution has exploded and continues to grow to this day. MGEs and the enzymes that enable their mobilization (transposases, recombinases, integrases, resolvases, invertases, etc.) have been adapted as useful experimental and therapeutic tools. But there is still much to be learned about MGEs, and in the age of next-generation sequencing we have more tools than ever before to interrogate their function. In chapter 2, this dissertation introduces software that analyzes next-generation sequencing data to identify integrative mobile genetic elements and to genotype the precise genomic location of their insertion with respect to a reference genome. This bioinformatics tool, called MGEfinder, is applied in an analysis of thousands of publicly-available bacterial genomes, and this analysis sheds light on how MGEs allow bacteria to adapt, develop antibiotic resistance, and become more virulent and dangerous to their human hosts. In chapter 3, this tool and others are then adapted and used as a part of a genomic data mining pipeline to identify novel genetic elements and enzymes that have promise as genome engineering tools. Thousands of these site-specific integrases (also described as recombinases) were identified and stored in a database, and they were curated and prioritized to identify those that hold promise as human genome editing tools, specifically. Early validation experiments are promising. In addition to studies that focus on this main theme of mobile genetic elements, this dissertation introduces additional works related to the identification of small open reading frames (smORFs) in microbial genomes (chapter 4), and the transcriptomic and epigenomic response of a colorectal cancer cell line to the microbial metabolite butyrate (chapter 5). Together, these chapters demonstrate the importance of developing and applying tools to the study of mobile genetic elements more broadly, indicating the great scientific and therapeutic potential of these ubiquitous genetic elements.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Durrant, Matthew George |
|---|---|
| Degree supervisor | Bhatt, Ami (Ami Siddharth) |
| Degree supervisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Bhatt, Ami (Ami Siddharth) |
| Thesis advisor | Montgomery, Stephen, 1979- |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Sherlock, Gavin |
| Degree committee member | Bassik, Michael |
| Degree committee member | Sherlock, Gavin |
| Associated with | Stanford University, Department of Genetics |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Matthew G. Durrant. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Matthew George Durrant
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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