Genetic research has advanced dramatically in recent years, progressing from enhancing food crops through genetic insights to exploring the possibility of resurrecting extinct species.
While the potential de-extinction of animals like the woolly mammoth or the Tasmanian tiger might be exciting in their own right, genetic studies still have a lot more to offer.
Today, scientists from The University of Hong Kong and Queen Mary University of London have accomplished what was once unthinkable: creating mouse stem cells—and ultimately a living mouse—without using any mouse DNA.
This was possible thanks to a single-celled organism, a choanoflagellate, whose ancient genes shed fresh light on the origins of multicellular life.
How To Build A Mouse From (Almost) Nothing
The groundbreaking November 2024 study—published in Nature Communications—harnessed the genetic potential of choanoflagellates to develop mouse stem cells capable of generating a living organism. Choanoflagellates are single-celled organisms and the closest living relatives of animals.
Central to this feat was the discovery of two transcription factors—Sox and POU—within the choanoflagellate genome. These factors are well-known in mammals for driving pluripotency, the ability of stem cells to transform into any cell type.
The Nobel Prize-winning work of Shinya Yamanaka in 2012 had already shown that expressing four key factors, including Sox2 and Oct4 (a POU gene), could reprogram differentiated cells into stem cells. The researchers simply pushed this concept further by replacing the native Sox2 gene in mouse cells with its choanoflagellate equivalent, demonstrating that these ancient genes could induce pluripotency.
The result was remarkable.
The reprogrammed cells were injected into a mouse embryo, resulting in a chimeric mouse with physical traits derived from both the donor embryo and the reprogrammed stem cells. Black fur patches and dark eyes were visible markers of this genetic integration, proving that the choanoflagellate-derived Sox genes could effectively replicate the function of mammalian stem cell genes.
Choanoflagellates Are Nature’s Genetic Time Capsules
Choanoflagellates are more than just single-celled organisms—they are living archives of the genetic toolkit that predates multicellular animals. As the closest living relatives to animals today, their genomes harbor versions of Sox and POU genes, which play pivotal roles in regulating cellular behavior.
These genes enable complex cellular processes, such as gene regulation and DNA binding, which are critical for multicellular development. While choanoflagellates do not possess stem cells, their Sox genes likely evolved to manage basic cellular functions.
Choanoflagellates can form multicellular colonies, which could have contributed to the gradual ... [+] evolution of multicellular life, rather than a single event that introduced multicellular beings.© Daniel Stoupin via Wikimedia Commons
Over time, these mechanisms were co-opted by multicellular organisms to facilitate the development of specialized cells and tissues. The discovery that these ancient genes can drive pluripotency in mice suggests that the genetic foundation for multicellularity was laid long before animals emerged.
The choanoflagellates’ ability to form multicellular colonies under certain conditions may have further supported the evolution of cooperative cell behaviors, setting the stage for multicellular life.
What Makes This Discovery So Important?
This research by the scientists at Queen Mary University of London and The University of Hong Kong is not just a technical marvel; it reshapes our understanding of evolution, genetics and the origins of multicellular life.
The discovery of pluripotent transcription factors in choanoflagellates challenges the long-held view that these genetic tools were innovations of multicellular organisms. This would mean that the transition from unicellular to multicellular life was not a leap requiring entirely new genes but rather an evolutionary refinement of existing genetic mechanisms.
The study highlights how ancient genes shared across species can serve fundamental roles despite vast evolutionary distances. The Sox and POU genes from choanoflagellates, separated from mice by nearly a billion years of evolution, retain the ability to drive pluripotency. This discovery underscores the deep genetic continuity that links all life on Earth.
The potential applications extend well beyond evolutionary biology.
Understanding how ancient transcription factors drive pluripotency could lead to novel approaches in regenerative medicine. By refining our ability to reprogram cells, researchers may develop more efficient therapies for repairing damaged tissues, treating degenerative diseases or even engineering new organs.
Finally, the study forces a reevaluation of how we view evolution itself. Rather than seeing complex traits as entirely new inventions, this research suggests that evolution often recycles and repurposes existing genetic tools to build complexity on the foundation of simplicity.
The creation of a mouse using ancient genes from a single-celled relative of animals is a testament to the ingenuity of nature. Do the wonders of the natural world draw you closer to all things green? Take a 2-minute quiz to see where you stand on theConnectedness to Nature Scale.