To Defend the Genome, These Cells Destroy Their Own DNA

Marie Delattre was studying the sexual reproduction practices of microscopic worms when she noticed something unexpected. Under the microscope, an embryo of the nematode Mesorhabditis belari was dividing as it should, progressing from one cell to two to four. But inside a few cells she saw an inexplicable spray of DNA fragments floating around where they didn’t belong.

“There was DNA everywhere, inside the nuclei and outside the nuclei — big chunks of DNA,” she said. “I thought it was a dead embryo.”

The embryo was not dead, but it was doing something that usually only dead cells do: destroying its genome. “I started to try to trace when these fragments appear, at what stage, and what they look like,” said Delattre, a cell biologist at the École Normale Supérieure in Lyon. “That’s how I figured out that this is not accidental. All the embryos did this.”

What Delattre had stumbled across, and what she and her lab described in a paper published in August in Current Biology, was an instance of programmed DNA elimination (PDE), in which organisms seem to purposefully eliminate portions of their genome. It’s an odd phenomenon that flies in the face of the precept that a genome is a vital, sacrosanct resource to be passed on faithfully to the next generation.

So far, researchers have identified PDE in only about 100 species across all branches of life: Single-celled ciliates with multiple nuclei do PDE; so do tiny worms, as well as the meters-long intestinal parasites of horses, many insects, and even songbirds. But PDE can be so difficult to spot that no one knows how common it really is. “It’s not very well known even among biologists,” Delattre said.

In addition to confirming the existence of another case of PDE, Delattre’s new paper also hints at an explanation for it. PDE points to a long-running fight between cells and DNA sequences that are of no use to their owner, or maybe even weigh it down. Like gardeners, cells must protect their genomes to remain functional and productive. What should a cell do when the weeds come in? The new study suggests that some species, like M. belari, might just pull the weeds out using PDE.

Despite its seeming novelty, PDE was discovered in the early days of molecular biology, long before researchers even knew that DNA is life’s genetic material. In 1887, the German biologist Theodor Boveri was studying the development of Parascaris, a nematode that parasitizes horses, when he witnessed its large genome coalesce, fragment and then reassemble into smaller portions during mitosis. The missing pieces were seemingly trashed without ceremony.

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