One of Evolution’s Biggest Moments Was Re-created in a Year

A unique experiment shows how multicellular organisms might have evolved from single-celled ancestors.

William Ratcliff

All the living things that we can see evolved from those that we can’t. Every human, bird, tree, and flower can trace its ancestry across a few billion years back to microscopic, single-celled organisms such as bacteria. That change from micro to macro, from one cell to many, was one of the most pivotal evolutionary journeys in Earth’s history. It is also among the hardest to imagine. Multicellular creatures, with their large size, complex body, and specialized tissues and organs, are so much more complicated than single-celled ones that it seems impossibly hard for the latter to turn into the former. But in fact, the process might have been “relatively simple,” William Ratcliff, an evolutionary biologist at Georgia Tech, told me. He and his team managed to replicate it in his laboratory in a matter of years.

In 2010, Ratcliff started working with brewer’s yeast, the single-celled fungus we use to make bread and beer. He repeatedly grew the yeast in liquid-filled tubes, shook them, and then used the cells that sank fastest to start new cultures. By favoring cells that stick together and settle faster, this simple procedure radically changed the yeast within just 60 days. Now whenever a cell divided in two, the new cells didn’t drift apart as they normally would; instead, they remained attached, creating beautiful, branching snowflakes that comprised dozens of cells. The yeast had evolved multicellularity in just two months.

But they then seemed stuck. Ratcliff had hoped that the snowflakes would continue getting bigger and more complex, but the annoyingly fragile entities never grew beyond a few hundred cells. Their branched shape was the problem: If any break can sever a large chunk off the main flake, that means “the strength of the group, no matter how big, is the strength of a single cell-cell connection,” Ratcliff told me. And once the snowflakes hit a certain size, “you look at them the wrong way, and they break.”

G. Ozan Bozdag, a member of Ratcliff’s team, solved the problem by depriving the snowflakes of oxygen. Scientists usually assume that oxygen is good for multicellularity, but because smaller organisms can use it more efficiently than larger ones, Bozdag reasoned that the latter might gain an advantage in the gas’s absence. He tested this idea with a new version of the shake-settle-and-seed experiment, which he started in 2018. For months, the oxygen-deprived snowflakes remained microscopic, but after a year or so, Bozdag could see the clusters with his own eyes. After 600 days of evolution, the snowflakes had become 20,000 times bigger, each containing half a million cells instead of just a few hundred. They now appeared as visible blobs, the largest of which were a millimeter wide—the size of fruit flies.

Together with physicist Peter Yunker, Ratcliff showed that the snowflakes busted through the size ceiling by lengthening each individual cell and strengthening the connections among cells. But more important, they evolved an entirely new structure, which the team saw using a powerful microscope. The branches had started wrapping around one another—less a radiating snowflake than a densely knotted mass of vines. This structure stops sections from easily breaking off and bestows incredible resilience: Yeast snowflakes are normally 100 times weaker than gelatin, but once entangled, they have the strength and toughness of wood. From what Ratcliff calls “dumb clumps of cells,” they had evolved what might reasonably be called a body.

“This is the most exciting study I’ve seen in a long time,” Leslie Babonis, an evolutionary biologist at Cornell University who was not involved in the study, told me. To her, it shows that the real challenge of multicellularity isn’t just keeping cells connected to their neighbors but keeping them strongly connected. Merely having a body is not enough; only when organisms have tough bodies that don’t readily fall apart can they evolve more complex traits such as specialized tissues and organs.

That’s what Ratcliff and his team have started to see. In the microscopic snowflakes, every cell behaves in much the same way, but in larger clusters, cells might perform one of at least three different roles: Some grow fast, others add sturdiness, and yet others self-destruct. (The latter might give the clusters a way of reproducing, by shedding small fragments into the environment.) The yeast have even evolved a way of moving fluid through their body, bringing nutrients to the cells deep inside them, and getting rid of waste.

A basic circulation, a life cycle, division of labor—these are all emergent traits that arise only once the yeast evolve strong bodies, and which cannot be predicted by studying any one constituent cell. They show that the snowflakes really are existing and evolving as multicellular organisms, as wholes that are more than the sum of their parts.

Throughout the history of life, multicellularity evolved on at least 25 independent occasions. Fungi may have done it much as Ratcliff’s yeast did, with small groups of cells that gained strength through entanglement. Animals, which had very different single-celled ancestors, probably became multicellular in a different way. But despite these differences, “every multicellularity story is going to be a version of the same basic process,” Ratcliff said. Single cells became groups, which could then become tough, which could then become big and complicated. “Look back through history, and you can’t imagine how animals evolved from a single-celled ancestor, because it’s such a big change,” Ratcliff said. “But that’s the beauty of this experiment: Every single change makes sense and looks straightforward.”

He doesn’t know what further changes are in store for the snowflake yeast, but he hopes to find out. Bozdag is still continuing the experiment; even during the early years of the coronavirus pandemic, he visited the team’s mostly shuttered lab every day to set up new generations. Ratcliff’s plan is to keep it going for decades, or “until we’re too old to keep doing it.”