A new study removes the air from a hypothesis linking early Earth’s oxygen supply to larger, more complex organisms. Georgia Tech researchers report a more complex effect

Scientists have long thought that there was a direct link between the rise in atmospheric oxygen, which began with the great oxygenation event 2.5 billion years ago, and the rise in large, complex multicellular organisms.

This theory, the “oxygen control hypothesis,” suggests that the size of these early multicellular organisms was limited by the depth to which oxygen could diffuse into their bodies. The hypothesis makes a simple prediction that has had a major impact in both evolutionary biology and geosciences: Larger atmospheric oxygen should always increase the size to which multicellular organisms can grow.

This hypothesis is difficult to test in a laboratory. However, a team of Georgia Tech researchers found a way – using directed evolution, synthetic biology, and mathematical modeling – to affect a simple multicellular life form called “snowflake yeast.” The results? Important new information on the links between early Earth oxygenation and the rise of large multicellular organisms – and it’s exactly how much O2 was available to some of our earliest multicellular ancestors.

“The positive effect of oxygen on the development of multicellularity is completely dose-dependent – the first oxygen enrichment of our planet would have severely restricted and not promoted the development of multicellular life,” explains G. Ozan Bozdag, researcher at the School of Biological Sciences and the lead author of the Study. “The positive effect of oxygen on the multicellular size can only be realized if it reaches high values.”

“Oxygen Suppression of Macroscopic Multicellularity” will be published in the May 14, 2021 issue of the journal Nature communication. Bozdag co-authors include Georgia Tech researcher Will Ratcliff, an associate professor in the School of Biological Sciences; Chris Reinhard, Associate Professor at the School of Earth and Atmospheric Sciences; Rozenn Pineau, Ph.D. Student at the School of Biological Sciences and the Interdisciplinary Graduate Program in Quantitative Biosciences (QBioS); together with Eric Libby, Assistant Professor at Umea University in Sweden and the Santa Fe Institute in New Mexico.

The yeast should develop in record time

“We show that the effect of oxygen is more complex than previously thought. The early rise in global oxygen should, in fact, severely limit the development of macroscopic multicellularity rather than select larger and more complex organisms, ”notes Ratcliff.

“People have long believed that oxygenating the surface of the earth was helpful for the development of large, complex multicellular organisms – some even believe it was a prerequisite,” he adds. “But nobody has ever tested this directly because we didn’t have a model system that could both go through many generations of evolution rapidly and grow over the full range of oxygen conditions,” from anaerobic conditions to modern levels.

However, the researchers succeeded in doing this with snowflake yeast, simple multicellular organisms that can change rapidly in evolution. By varying their growing environment, they developed over 800 generations of snowflake yeast in the laboratory with a selection for larger sizes.

The results surprised Bozdag. “I was amazed to see that multicellular yeasts doubled in size very quickly when they couldn’t use oxygen, while populations that evolved in a moderately oxygenated environment showed no increase in size at all,” he says. “This effect is robust – even over much longer periods of time.”

Size – and oxygen levels – are important for multicellular growth

In the team’s research, “a large size easily evolved, either when our yeast had no oxygen or a lot of it, but not when it was low in oxygen,” says Ratcliff. “We have done a lot more work to show that this is indeed a completely predictable and understandable result of the fact that oxygen, when limited, acts as a resource. When cells have access to it, they get great metabolic benefits. When oxygen is scarce, it cannot diffuse very far into organisms. Hence, there is an evolutionary incentive for multicellular organisms to be small – which allows most of their cells to have access to oxygen – a limitation that does not exist when oxygen is simply not available or when there is enough of it to go deeper into tissue diffuse. “

Ratcliff says his group’s work not only challenges the oxygen control hypothesis, but also helps science understand why so little obvious evolutionary innovations took place in the world of multicellular organisms in the billions of years after the great oxygenation event. Ratcliff explains that geologists refer to this period as the “Boring Billion” in Earth’s history – also known as the Most Boring Time in Earth’s History and Middle Ages – a period when oxygen was present in the atmosphere, but in small amounts and multicellular Organisms remained relatively small and simple.

Bozdag adds another glimpse into the uniqueness of the study. “Previous work examined the interplay between oxygen and multicellular size mainly using the physical principles of gas diffusion,” he says. “While this reasoning is essential, we also need a full consideration of the principles of Darwinian evolution when examining the origins of the complex multicellular life on our planet.” Bozdag adds that researchers were finally able to propel organisms through many generations of evolution to do just that.


Citation: Bozdag, GO, E. Libby, R. Pineau et al., “Oxygen suppression of macroscopic multicellularity”. ((Nat Commun 12, 2838 2021). https: //.doi.org /10.1038 /s41467-021-23104-0

This work was supported by National Science Foundation Grant No. DEB-1845363 to WCR, NSF Grant No. IOS-1656549 to WCR, NSF permit no. IOS-1656849 to EL and a Packard Foundation Science and Technology grant to WCRCTR and WCR confirm funding from the NASA Astrobiology Institute.

The Georgia Institute of Technology, or Georgia Tech, is one of the top 10 public research universities developing leaders who advance technology and improve the human condition. The institute offers degrees in business, computers, design, engineering, humanities, and natural sciences. The nearly 40,000 students from 50 states and 149 countries study on the main Atlanta campus, at locations in France and China, and through distance and online learning. As a leading technology university, Georgia Tech is a driver of economic development for Georgia, the Southeast and the nation, conducting more than $ 1 billion in research annually for government, industry and society.


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