In the tide pools of Monterey, California, a tiny organism is rewriting our understanding of evolution.
We've long understood that natural selection operates on individuals—the fastest cheetah catches more prey, the tallest tree captures more sunlight. But what if evolution works at a much deeper, more fundamental level? What if individual cells within our bodies compete for evolutionary dominance?
Botryllus schlosseri is one of our closest invertebrate relatives, sharing a common ancestor with vertebrates like ourselves 2 .
Colonial ascidians possess a basic chordate body plan during their larval stage, complete with a notochord and nerve cord.
Botryllus schlosseri isn't your typical lab animal. At first glance, it looks more like a beautiful mosaic flower etched onto coastal rocks than an animal. But this colonial ascidian holds an extraordinary biological secret: it's one of our closest invertebrate relatives, sharing a common ancestor with vertebrates like ourselves 2 .
What makes Botryllus so fascinating to scientists is its dual life strategy:
Produces tadpole-like larvae with the basic chordate body plan (complete with a notochord and nerve cord) 4 .
Creates genetically identical clones through budding, forming expansive colonies 4 .
Each colony consists of multiple individuals (zooids) embedded in a shared gelatinous tunic, connected by a network of blood vessels that extends throughout the entire colony . This unusual arrangement sets the stage for some remarkable biology.
When two Botryllus colonies grow close together, something extraordinary can happen. The blood vessels at their edges may fuse, creating a natural parabiosis—the two colonies become one interconnected system, sharing a circulatory system .
But this fusion doesn't always occur. Whether colonies fuse or reject each other depends on a single highly polymorphic histocompatibility gene called Botryllus histocompatibility factor (BHF). With hundreds of possible variants in the wild, colonies only fuse if they share at least one BHF allele 1 .
This fusion mechanism creates a biological arena where cellular competitions play out—with evolutionary consequences far beyond what scientists initially imagined.
While studying these fused colonies, researchers noticed something puzzling. When they examined colonies that had been fused for extended periods, they discovered that the germline (reproductive cells) often belonged to only one of the original partners. Even more surprisingly, sometimes the "losing" colony would be completely resorbed, yet its germline would live on in the winning colony's body .
This suggested something remarkable: stem cells from one colony could travel through the shared bloodstream, invade the other colony, and outcompete the resident stem cells for access to the gonads 1 .
Through careful experimentation, scientists discovered that these stem cell competitions follow predictable patterns. Some colonies consistently dominate others in both germline and somatic competitions, while others show mixed patterns—winning in germline but losing in somatic tissues, or vice versa .
| Colony Combination | Germline Competition Winner | Somatic Competition Winner | Notes |
|---|---|---|---|
| F + G | F | G | Mixed outcome |
| F + B | F | B | Mixed outcome |
| G + B | G | G | Complete dominance |
| F + B + G | F | G | Hierarchy maintained |
These competitions aren't random—they're governed by intrinsic properties of the stem cells themselves, creating predictable hierarchies that persist even in complex multi-colony chimeras .
To prove that stem cells themselves—rather than some other factor—were responsible for these competitions, researchers designed an elegant transplantation experiment 1 . The question was straightforward: if you isolate stem cells from a colony known to be a "germline winner," can they take over the germline of a "loser" colony?
Researchers prospectively isolated a population of multipotent, self-renewing stem cells from Botryllus colonies 1 .
They selected donor-recipient pairs where the donor colony was known to dominate germline competitions against the recipient type.
The isolated stem cells were injected directly into the circulatory system of recipient colonies.
Using genetic markers, they tracked whether the transplanted stem cells could establish themselves in the recipient's gonads and produce gametes.
The transplanted stem cells retained their competitive phenotype—cells from "winner" colonies would indeed take over the germline of "loser" colonies. Even more remarkably, these stem cells contributed to either somatic or germline fates, but not both, suggesting separate lineages or context-dependent differentiation 1 .
This experiment provided the smoking gun: stem cells themselves are the units of selection, carrying their competitive abilities with them when transplanted.
Studying stem cell competitions in Botryllus requires specialized materials and approaches. The table below highlights key reagents and their applications in this fascinating field:
| Reagent/Material | Primary Function | Research Application |
|---|---|---|
| Genetic markers (dinucleotide repeats, LINE elements, single-gene polymorphisms) | Track cell lineages across colonies | Identifying origin of somatic tissues and gametes in chimeras |
| Histocompatibility testing | Determine fusion compatibility | Predicting which colonies will fuse or reject |
| Stem cell transplantation apparatus | Deliver stem cells to recipient colonies | Testing competitive potential of isolated stem cells |
| Vascular access methods | Access shared circulatory system | Introducing cells or tracking dyes into blood |
| BHF gene sequencing | Analyze histocompatibility genetics | Understanding genetic basis of fusion/rejection |
The discovery that stem cells serve as units of natural selection has profound implications for evolutionary biology. It suggests that evolution operates at multiple levels simultaneously—not just between individuals, but between cell lineages within those individuals .
This perspective helps explain why histocompatibility systems like BHF evolved to such extraordinary complexity. By limiting stem cell parasitism to close kin (who likely share the same histocompatibility alleles), Botryllus prevents its germline from being hijacked by completely unrelated individuals 1 . This maintains genetic diversity across the population while allowing competitions among relatives.
Evolution operates simultaneously at individual and cellular levels.
Perhaps the most medically relevant insight comes from understanding how these principles apply to human diseases. The same competitive dynamics observed in Botryllus stem cells appear to operate in our own bodies .
Researchers have found that in mice and humans, blood-forming stem cells compete for bone marrow niches. The progression from normal blood cell development to leukemia often involves successive competitions between genetically distinct stem cell clones, with the fittest clones eventually dominating .
This suggests that cancer may represent a hijacking of the same stem cell competition mechanisms that evolved for legitimate evolutionary purposes. Understanding how stem cell competitions are normally regulated in Botryllus could provide vital clues for controlling abnormal cell competitions in human disease.
The humble colonial ascidian has taught us a revolutionary lesson: natural selection operates at the level of stem cells. These remarkable cells aren't just passive building materials—they're active participants in evolutionary processes, competing for the ultimate prize of genetic immortality.
This discovery bridges multiple biological disciplines, connecting evolutionary theory with stem cell biology and cancer research. It demonstrates how studying seemingly obscure organisms can reveal fundamental biological principles with far-reaching implications.
As research continues, scientists are now asking new questions: What molecular mechanisms determine which stem cells win these competitions? How did these systems evolve? And what can stem cell competitions in Botryllus teach us about controlling similar competitions in human diseases?