Sometimes, the most significant scientific discoveries happen by accident.
Scientists have long known that whole-genome duplication (WGD) — the process by which organisms copy all their genetic material — plays an important role in evolution. But understanding just how WGD arises, persists, and drives adaptation has remained poorly understood.
In an unexpected turn, scientists at Georgia Tech not only uncovered how WGD occurs, but also how it stays stable over thousands of generations of evolution in the lab.
The new study was led by William Ratcliff , professor in the School of Biological Sciences, and Kai Tong, a former Ph.D. student in Ratcliff's lab who is now a postdoctoral fellow at Boston University.
Their paper, " Genome duplication in a long-term multicellularity evolution experiment ," was published in Nature as the journal's cover story in March.
"We set out to explore how organisms make the transition to multicellularity, but discovering the role of WGD in this process was completely serendipitous," said Ratcliff. "This research provides new insights into how WGD can emerge, persist over long periods, and fuel evolutionary innovation. That's truly exciting."
A secret hidden in the data
In 2018, Ratcliff's lab launched an experiment to explore open-ended multicellular evolution. The Multicellular Long-Term Evolution Experiment (MuLTEE) uses "snowflake" yeast (Saccharomyces cerevisiae) as a medium, evolving it from a single cell to increasingly complex multicellular organisms. The researchers do this by selecting yeast cells for larger size on a daily basis.
"These long-term evolution studies help us answer big questions about how organisms adapt and evolve," said Tong. "They often reveal the unexpected and expand our understanding of evolutionary processes."
That's exactly what happened when Ozan Bozdag, a research faculty member in Ratcliff's lab, noticed something unusual in the snowflake yeast. Bozdag observed the yeast when it was 1,000 days old and saw characteristics suggesting it might have gone from diploidy (having two sets of chromosomes) to tetraploidy (having four).
Decades of lab experiments show that tetraploidy is characteristically unstable, reverting back to diploidy within a few hundred generations. For this reason, Tong was skeptical that WGD had occurred and persisted for thousands of generations in the MuLTEE. If true, it would be the first time a WGD arose spontaneously and persisted in the lab.
After taking measurements of the evolved yeast, Tong found that they had duplicated their genomes very early — within the first 50 days of the MuLTEE. Strikingly, these tetraploid genomes persisted for more than 1,000 days, continuing to thrive despite the usual instability of WGD in laboratory conditions.
The team discovered that WGD arose and stuck around because it gave the yeast an immediate advantage in growing larger, longer cells and forming bigger multicellular clusters, which are favored under the size selection in the MuLTEE.
Further experiments showed that while WGD in snowflake yeast is normally unstable, it persisted in the MuLTEE because the larger, multicellular clusters had a survival advantage. This stability allowed the yeast to undergo genetic changes, with aneuploidy (the condition of having an abnormal number of chromosomes) playing a key role in the development of multicellularity. As a result, MuLTEE became the longest-running polyploidy evolution experiment, offering new insights into how genome duplication contributes to biological complexity.
A MuLTEE-talented team
Ratcliff emphasized that rigorous undergraduate research played a critical role in their unexpected breakthrough. Four undergraduate students were integral to the success of the experiment, joining the research early in their education at Georgia Tech.
"This kind of authentic research experience is life-changing and career-altering for our students," Ratcliff said. "You can't get this level of learning in a classroom."
Vivian Cheng, who joined Ratcliff's lab as a first-year and graduated in 2022, took on the challenge of genetically engineering diploid and tetraploid yeast strains along with another student. Ratcliff and Tong ended up using these same strains as a major part of their analysis.
"This work is another step toward understanding the various factors that contribute to the evolution of multicellularity," said Cheng, now a Ph.D. candidate at the University of Illinois Urbana-Champaign. "It's super cool to see how this single factor of ploidy level affects selection in these yeast cells."
Ratcliff notes that some of his team's most significant findings could never have been anticipated when they started MuLTEE. But that's the whole point, he says.
"The most far-reaching results from these experiments are often the ones we weren't aiming to study, but that emerge unexpectedly," he added. "They push the boundaries of what we think is possible." He and assistant professor James Stroud expanded upon this theme in a review of long-term experiments in evolutionary biology , published in the same issue of Nature.
This discovery sheds new light on the evolutionary dynamics of whole-genome duplication and provides a unique opportunity to explore the consequences of such genetic events. With its potential to fuel future discoveries in evolutionary biology, this work represents an important step in understanding how life evolves on both a short-term and long-term scale.
"Scientific progress is seldom a straightforward journey," Tong said. "Instead, it unfolds along various interconnected paths, frequently coming together in surprising ways. It's at these crossroads that the most thrilling discoveries are made."
Note: Ozan Bozdag, Sayantan Datta, Daniella Haas, Saranya Gourisetti, Harley Yopp, Thomas Day, Dung Lac, Peter Conlin, and Ahmad Khalil also played major roles in this experiment.
Funding: The U.S. National Institutes of Health (NIH), Human Frontiers Science Program, and the Packard Fellowship for Science and Engineering.
Citation: Tong, K., Datta, S., Cheng, V. et al. Genome duplication in a long-term multicellularity evolution experiment. Nature (2025).
DOI: https://doi.org/10.1038/s41586-025-08689-6
