Nature Study: Molecular Switch Controls Cell Transitions

Nagoya University


Scientists at Nagoya University in Japan have identified the genes that allow an organism to switch between living as single cells and forming multicellular structures. This ability to alternate between life forms provides new insights into how multicellular life may have evolved from single-celled ancestors and eventually led to complex organisms like animals and plants.

Published in Nature , the study represents an exceptionally detailed molecular explanation of how clonal multicellularity, where all cells descend from a single ancestor, can be achieved and controlled at the genetic level.

Flexible life forms dependent on food availability

The research team led by Professor Gohta Goshima at Nagoya University's Sugashima Marine Biological Laboratory identified the genes that control this cellular switch in the black marine yeast Hortaea werneckii.

They observed that when nutrients are abundant, H. werneckii cells multiply and remain attached as multicellular bodies. However, when nutrients become scarce, cells divide by budding and live separately as individuals, allowing them to move through the water to find new nutrient-rich locations. This flexibility may provide a survival advantage in the unpredictable ocean environment where nutrient availability constantly changes.

To understand the genetic basis of this switching ability, the team isolated mutants that had lost the ability to switch and identified which genes were disrupted in them. This revealed 10 key genes controlling the switch.

When they deleted a specific gene, the yeast lost its switching ability and became stuck as either single cells or multicellular bodies. But when researchers deleted another gene in addition to the first, the yeast regained its ability to switch back and forth. This suggests that there are multiple genetic pathways to achieve the same flexibility.

"We found that a protein called Myb1 acts as a master switch and controls the change between cellular states. When Myb1 levels are high, cells bud and separate, but when this protein is degraded in nutrient-rich conditions, cells form multicellular structures," Professor Goshima explained.

Some of the genes identified were known to help fungi make spores, but H. werneckii evolved to use these same genes for switching between single cells and multicellular forms. This gene recycling may be a common evolutionary strategy for developing new traits.

Multicellular, bigger bodies to prevent being swept away

The research team also isolated multicellular-prone strains of H. werneckii and interestingly they were all found on the surface of marine animals like sponges and corals. These environments are known to be nutrient-rich due to symbiotic bacteria. The researchers hypothesize that forming a multicellular body helps the yeast stay anchored in favorable, nutrient-rich locations and resist being washed away by water currents.

Laboratory experiments supported this idea: when unicellular and multicellular strains were mixed and exposed to simulated water flow, the multicellular bodies tended to stay attached to the surface, while unicellular cells were washed away.

Evolution takes different paths in related species

In addition to identifying the switching genes in H. werneckii, the study examined related yeast species and found that the genetic mechanisms for switching are not completely conserved across evolution.

Related species show different patterns. In some species these genes appear not to function as switches but instead evolved alternative mechanisms. Others completely lost their switching ability and became either permanently multicellular or unicellular.

"An example is a related yeast species, Neodothiora pruni, that can also switch between single cells and multicellular forms. When we compared the two species, we found most genes worked the same way. However, Myb1 was essential only in H. werneckii, so closely related species can evolve different genetic solutions for the same behavior."

Professor Goshima's future research will investigate what drives this evolutionary diversity and how simple multicellular forms might develop into more complex structures.

"What we achieved was controlling unicellularity and simple multicellularity, but the next obvious step is whether simple multicellularity becomes more complex multicellularity," he said.

The ease with which single mutations can eliminate or restore cellular flexibility suggests that the transition between unicellular and multicellular forms may have occurred repeatedly throughout evolutionary history.

"H. werneckii is now a valuable research tool for scientists who study how multicellular life evolved. The ability to switch between single cells and multicellular forms may have been an evolutionary stepping stone before organisms became permanently multicellular," Professor Goshima noted.

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