Scientists uncover key mechanisms in evolution: Whole-genome overlap promotes long-term adaptation

Sometimes the most important scientific discoveries happen by chance. Scientists have long known that whole-genome overlap (WGD) (the process by which an organism copies all genetic material) plays an important role in evolution. However, understanding how WGD occurs, persists and promotes adaptation remains poorly understood.

In the unexpected turn, scientists at Georgia Tech not only revealed how WGD occurs, but also revealed that it remains stable across thousands of generations of evolution in the lab.

The new research was led by William Ratcliffe, a professor in the Faculty of Biological Sciences, and former PhD Kai Tong. He is a student in the lab at Ratcliffe, currently a postdoctoral researcher at Boston University.

Their paper, “Genome overlap in long-term multicellular evolutionary experiments,” was published in nature in March as a cover story for the journal.

“We set out to explore how organisms make the transition to multicellularity, but discovering the role of WGD in this process was entirely by chance,” Ratcliffe said. “This study provides new insights into how WGD emerges, lasts for a long period of time, and fuel evolutionary innovations are possible. It’s really exciting.”

Secrets hidden in the data

In 2018, Ratcliff’s lab began experiments exploring open-ended multicellular evolution. Multicellular Long-Term Evolution Experiments (Multee) use “snowflake” yeast (Saccharomyces cerevisiae) as a medium to evolve from a single cell to an increasingly complex multicellular organism. Researchers do this by selecting yeast cells for larger sizes each day.

“These long-term evolutionary studies will help answer big questions about how organisms adapt and evolve,” Ton said. “They often reveal unexpected things and broaden their understanding of the evolutionary process.”

That’s exactly what happened when Ozan Bozdug, a research faculty member in Ratcliffe’s lab, noticed something unusual in snowflake yeast. Bozdag observed properties that suggested that yeasts could have turned from diploid (having two sets of chromosomes) to tetraploid (having four chromosomes).

Decades of lab experiments show that tetraploids are characteristically unstable and return to diploids within hundreds of generations. For this reason, Tong was skeptical that the WGD had occurred and lasted multi-tee for thousands of generations. If true, this is the first time that WGD has been spontaneously occurring and persisted in a lab.

After taking measurements of evolved yeast, Tong discovered that he replicated the genome very quickly in the first 50 days of mulch. Surprisingly, these tetraploid genomes lasted more than 1,000 days and continued to thrive despite the normal instability of WGD in laboratory conditions.

The team discovered that WGD was stranded. This is because Yeast quickly gave an advantage in growing larger, longer cells and forming larger multicellular clusters that are preferred under multi-size selection.

Further experiments have shown that WGD in snowflake yeast is usually unstable, but that it lasts multi-cellular clusters as they have survival advantages. This stability allowed yeast to undergo genetic alterations, and aneuploidy (a condition with an abnormal number of chromosomes) played an important role in multicellular development. As a result, Multee became the longest-running ploidy evolutionary experiment, providing new insights into how genome overlap contributes to biological complexity.

A versatile team

Ratcliffe emphasized that rigorous undergraduate studies played an important role in unexpected breakthroughs. Four undergraduates were crucial to the success of the experiment and participated in the study early in their education at Georgia Tech.

“This kind of authentic research experience is a life-changing career change for students,” Ratcliffe said. “You can’t get this level of learning in the classroom.”

Vivian Cheng, who joined Ratcliffe’s lab for his first year and graduated in 2022, took on the challenge of genetically engineered diploid and tetraploid yeast strains along with another student. Ratcliffe and Ton ended up using the same strains as most of the analysis.

“This work is another step in understanding the various factors that contribute to the evolution of multicellularity,” he said, and now has a PhD. Candidate for the University of Illinois Urbana-Champaign University. “It’s very cool to see how this single ploidy level affects the selection of these yeast cells.”

Ratcliffe points out that some of his team’s most important findings would never have been expected when they started multi. But that’s the whole point, he says.

“The most extensive results from these experiments are often those we weren’t aiming to study, but it shows unexpectedly,” he added. “They push the boundaries of what we think is possible,” he and Assistant Professor James Stroud expanded the subject 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 replication and provides a unique opportunity to explore the consequences of such genetic events. Because it may facilitate future discoveries in evolutionary biology, this study represents an important step in understanding how life evolves on both short-term and long-term scales.

“Scientific progress is rarely an easy journey,” Tong said. “Instead, it unfolds along a variety of interconnected paths and frequently gathers in amazing ways. It is at these intersections that make the most thrilling discoveries.”