Impact of de novo transposition on the Drosophila melanogaster genome: effects on the 3D nuclear architecture and telomere dynamics

Human cells package meters of DNA into a micron-sized nuclei through a series of specific looping structures while still preserving biological functions. Impinging on this process is the complexity and structure of the human genome. For example, the human genome has constantly been invaded by selfish elements called transposons. Transposons are fragments of DNA that regularly propagate and change locations throughout the genome to the point that over half the human genome is composed of these elements. Adding to the complexity, each human chromosome is capped by specialized DNA and protein structures called telomeres. How cells achieve a state of compressed genome, repressed transposons, and protected telomeres remains poorly understood. Errors in any of these processes have consequential impacts on human health including effects on diseases, aging, and cancer. My research fills in the gaps with genomic studies and the development of a novel computational algorithm that was used to quantify the 3D spatial organization of the fruit fly, mouse, and human genomes. These advances provide novel biological insights into the causes and consequences of 3D nuclear organization. Using fruit flies as a model system I tracked the dynamics of transposons and telomeres over many generations. To add context and capture natural variation, I also analyzed populations from around the world. By doing so I was able to quantify the rates of change, the influence on the genome structure, and the non-canonical mechanisms of regulation of these foundational components of genomes.