2025 Theses Doctoral

Co-option of transposable elements for RNA-guided DNA integration, rearrangement, and regulation

Walker, Matt

Transposable elements (TEs) are often described as selfish genetic elements that are primarily driven by their own propagation. However, there are numerous instances wherein the genes encoded by TEs have become domesticated and confer substantial advantages to their hosts.

In this thesis, I explore three remarkable biological processes in which TE-encoded genes have been repurposed. First, I study TE co-option by CRISPR-Cas machinery to perform RNA-guided DNA integration, illuminating the specific DNA requirements for mobilization by the transposase TnsB and uncovering the involvement of a new cellular factor in efficient transposition (Chapter 2).

Next, I investigate a family of transposases that have been repurposed to perform DNA elimination during cellular development of the ciliate Oxytricha trifallax, probing the sequence specificity of these transposases and revealing the minimal sequence requirements for target DNA recruitment and cleavage (Chapter 3).

Finally, in my work on RNA-guided flagellin regulation, I study how bacterial viruses (bacteriophages) have co-opted the TE-encoded gene TnpB to perform transcriptional regulation of their bacterial hosts (Chapter 4). I uncover the biological effects of this regulatory system, finding that it dramatically transforms the host flagellar composition to enhance cellular motility, mammalian immune evasion, and gut colonization.

Altogether, this thesis presents three striking instances of TE-encoded genes being repurposed for new functions, highlighting the evolutionary versatility of TEs in shaping biological processes and expanding our understanding of genomic complexity and evolution.