While we commonly assume that individual organisms carry an identical genome across cells and tissues, a number of eukaryotic species undergo Programmed DNA Elimination (PDE), the destruction of parts of chromosomes in somatic cells during normal development. How and why PDE occurs has remained largely unresolved, largely due to a lack of lab-tractable models and insufficiently complete sequencing data (e.g., high-fidelity long-reads).

We recently discovered that species of Mesorhabditis, a genus of lab-tractable nematode worms, undergo substantial PDE during early development (~30% of the genome is eliminated). In this talk, I will first introduce how we are probing the PDE process in Mesorhabditis using both experimental and computational approaches. I will then focus on how, using a combination of PacBio Hi-Fi, Illumina and Hi-C data, we could resolve elimination breakpoints and identify a clear sequence motif specifying genome cutting. Surprisingly, we then found that a majority of these motifs are located inside transposable elements (TEs), and that some breakpoint motifs have moved recently under TE control.

I will end by discussing our ongoing search for the effector nuclease(s) of PDE and whether it is TE-encoded, and the evolution of PDE including, ultimately, whether PDE benefits the host or is a TE-encoded ‘selfish' process.