Yeast shows physics can give rise to multicellular life sans mutations

By the time Nishant Narayanasamy joined Shashi Thutupalli’s lab at the National Centre for Biological Sciences (NCBS) in Bengaluru in 2019, the lab had a new guest: a yeast colony that had seemingly grown way beyond its expected size.

The snowflake yeast had been shipped from William Ratcliff’s laboratory at the Georgia Institute of Technology in the U.S. Regular yeast — the same organism that makes cakes fluffy — grows as a single cell. When it reaches a certain size, a small bump appears on its surface. The yeast’s nucleus, the compartment that holds its genetic material, splits into two and moves into this bud. The bud grows until it reaches a certain size and eventually falls off from the parent, making new yeast.

But a small change in snowflake yeast’s genetic composition prevents the bud from falling off. As newer buds appear, the yeast clusters in the shape of a snowflake. And as the cluster grows, in about 12 hours it becomes a large blob visible to the naked eye.

Snowflake yeast has been used to study how lifeforms first became multicellular. Multicellular organisms can grow much larger than those with only one cell — as long as they can deal with the other effects of largeness. For example, how does the organism ensure all cells in its body receive the nutrients they need to grow?

This is why most animals and plants evolved specific structures to transport nutrients. Blood and blood vessels do this job in humans.

A simple process

Snowflake yeast has no such facility, however, which means at some point the yeast should stop growing. Any further increase in size would cause at least some of its cells to not get enough nutrients. However, defying expectations, the snowflake yeast in Thutupalli’s lab continued to grow — that too at an exponential rate. How the yeast attained this feat was a mystery.

Narayanasamy and Thutupalli, along with a team from Georgia Tech, reported in the June 2025 issue of Science Advances a mechanism by which the yeast can ensure all its cells receive nutrients, even when the cluster is big. In the absence of a biological structure, the yeast continue to grow thanks to a simple physical process, the authors wrote in their paper.

The implications of the work go beyond how yeast grows. The work “offers support to an unconventional view of how major changes are initiated in evolution,” Vidyanand Nanjundiah, an evolutionary biologist and a professor at the Centre for Human Genetics, Bengaluru, said. He wasn’t associated with the study.

The consensus among scientists is that multicellular organisms evolved billions of years ago when mutations accumulated over time. But Narayanasamy’s and Thutupalli’s work suggests physical and chemical phenomena alone could have helped unicellular organisms evolve into multicellular ones before genetic changes came into the picture.

Flowing into multicellularity

In a lab, yeast can be grown in either a solution or a jelly-like substance that contains all its nutrients. Narayanasamy and Thutupalli observed that large clusters of snowflake yeast continue to grow exponentially only when kept in the solution. It seemed being surrounded by a fluid was crucial.

Diffusion is one way in which nutrients move through a fluid: the particles moving from a place in which their concentration is higher to one where it’s lower. But Narayanasamy and Thutupalli knew from previous work that diffusion alone couldn’t account for the size of large snowflake yeast clusters. Per their estimate, diffusion can explain the growth of these clusters only up to a size of about 50 micrometers (µm) whereas their clusters could grow up to 20x larger.

So they hypothesised that a different process is at play: advection, when the fluid itself moves around, carrying with it the dissolved nutrients. To test their hypothesis, they added to the solution small particles coated with a dye that glows in blue light. Using a microscope to trace how these particles moved in the solution could help them visualise the flow of the fluid.

They added a snowflake yeast cluster to this solution and let it grow. The duo observed that as the cluster expanded, the solution around it moved inside the cluster from its sides, then escaped from the top.

A natural motor

Some unicellular organisms can make fluids flow using specialised hair- or whip-like structures called cilia or flagella. Snowflake yeast have neither. This is where physics becomes important.

When snowflake yeast clusters grow, they consume glucose from the solution. This reduces the density of the solution in places where it surrounds the yeast. The cluster also produces alcohol and carbon dioxide, both of which are less dense than the solution, according to the paper.

Fluids that are less dense — in this case the surrounding solution depleted of glucose and enriched with alcohol and carbon dioxide — rise above the rest of the solution. The team reasoned the flow it observed resulted from the same principle: as the cluster consumed the sugar and produced alcohol and carbon dioxide in the solution, the solution’s density dropped. This fraction spontaneously moved upward, generating the flow that kept the yeast cluster alive and growing.

To confirm this, the duo checked whether flows were present around clusters that are dead and not actively consuming sugar. They didn’t find any, and concluded the living clusters metabolising sugar from the solution created the flows.

A different view of evolution

Biologists have used snowflake yeast clusters as a model to study how multicellular organisms evolved from unicellular ones. Contrary to the view with genetic changes, the new study supports the idea that “multicellularity could originate and be maintained initially solely on the basis of physics and chemistry, with no genetic change,” Nanjundiah said. “A later genetic change could then have made multicellularity inevitable in the … living beings of today,” he added.

The next step for him is to check if such a change subsequently occurs in the yeast, rendering multicellularity a part of its biological blueprint.

Gautam Menon, a professor of physics and biology at Ashoka University in Sonepat, called the study “fascinating” and the alternative model “temptingly attractive”.

As researchers wait for more evidence of this model, the NCBS team is investigating whether these flows can account for other major evolutionary changes: the ability of organisms to move, for example.

Experiments on snowflake yeast have something more to teach about the nature of biology, Thutupalli said. “There may not exist any organism in the wild that generates flows by such a mechanism,” he said, “but biology, in its much larger sense, can do it.”

This is why, he added, our view of biology must extend beyond what we see in the natural world to novel phenomena that may occur only in the laboratory. “These may or may not happen outside [the lab] but they are genuinely a feature of livingness — of biology.”

Sayantan Datta is a science journalist and a faculty member at Krea University.