In a lab at Queen Mary University of London, a mouse was born whose existence defied conventional biology. It carried within its cells the ancient genetic legacy of a single-celled creature, one whose lineage diverged from ours nearly a billion years ago. These are genes that predate animals.
The achievement bridges nearly a billion years of evolutionary history and challenges our assumptions about what makes us — and the stem cells that build us — distinctly animal.
“This study implies that key genes involved in stem cell formation might have originated far earlier than the stem cells themselves, perhaps helping pave the way for the multicellular life we see today,” said Dr. Alex de Mendoza of Queen Mary University of London, a lead author of the research.
The Ancient Blueprint for Pluripotency
The work was made possible through a collaboration between Dr. de Mendoza and researchers at the University of Hong Kong. Together, they demonstrated that ancient versions of genes found in choanoflagellates, single-celled organisms that share a common ancestor with animals, could reprogram normal mouse cells into pluripotent stem cells — the kind of stem cells that are capable of developing into any type of cell.
Stem cells are essential for animal development. They have the unique ability to renew themselves and specialize into diverse cell types. The specialized cells in your liver, skin, and brain all first started from a stem cell. In animals, this process is controlled by transcription factors like Sox2 and Oct4, which regulate the genes responsible for pluripotency. Until now, researchers believed these factors were biological innovations exclusive to animals.
Choanoflagellates, often described as “living fossils,” are our closest single-celled relatives. Although they’re not nearly as complex as multicellular animals, their genomes contain ancient versions of Sox and POU genes.
These genes, it turns out, may have been repurposed over evolutionary time.
“Choanoflagellates don’t have stem cells,” Dr. de Mendoza explained. “They’re single-celled organisms, but they have these genes, likely to control basic cellular processes that multicellular animals probably later repurposed for building complex bodies.”
To test this idea, the team replaced the native Sox2 gene in mouse cells with a choanoflagellate version. Remarkably, these modified cells were able to reprogram into pluripotent stem cells. The researchers then injected these cells into a developing mouse embryo. The resulting chimeric mouse bore distinctive traits like black fur patches and dark eyes. This confirmed that the ancient genes could integrate seamlessly into the animal’s development even after a billion years since they first likely appeared.
“By successfully creating a mouse using molecular tools derived from our single-celled relatives, we’re witnessing an extraordinary continuity of function across nearly a billion years of evolution,” said Dr. de Mendoza.
This is a feat previously thought achievable only by modern animal Sox proteins.
However, the POU factors from choanoflagellates showed distinct limitations. While these proteins could bind DNA, their specificity differed from the Oct4 proteins in animals, rendering them incapable of inducing pluripotency. This may be a hint that may point scientists to the evolutionary changes that were truly crucial for the emergence of animal stem cells.
Rewriting the Timeline of Stem Cells
These discoveries shift our understanding of the evolutionary trajectory leading to multicellular life. The presence of functional Sox and POU genes in unicellular organisms suggests that the groundwork for complex cellular systems was laid long before the first animals appeared.
There may even be some interesting practical applications. By showing that genes from single-celled ancestors can perform critical roles in modern stem cell machinery, scientists have opened the door to new therapies in regenerative medicine.
“Studying the ancient roots of these genetic tools lets us innovate with a clearer view of how pluripotency mechanisms can be tweaked or optimised,” said Dr. Ralf Jauch of the University of Hong Kong.
Synthetic versions of these ancient genes could someday outperform their animal-derived counterparts in stem cell therapies, potentially accelerating the repair of damaged tissues or the treatment of degenerative diseases.
This finding also highlights evolution’s uncanny knack for recycling. The early versions of Sox and POU proteins may have helped choanoflagellates regulate fundamental cellular functions. Over time, these same genes were co-opted to build the sophisticated architectures of multicellular animals.
It’s a reminder of how life’s building blocks often transcend the boundaries we impose on them. “By successfully creating a mouse using molecular tools derived from our single-celled relatives, we’re witnessing an extraordinary continuity of function across nearly a billion years of evolution,” said Dr. de Mendoza.
The research is as much a journey backward in time as it is a leap forward. And that’s pretty awesome, if you ask me.
The findings were reported in the journal Nature Communications.
