New research suggests rainwater could have helped form the first protocell walls

One of the major unanswered questions about the origin of life is how droplets of RNA floating around the primordial soup turned into the membrane-protected packets of life we call cells.

A new paper by researchers with the University of Chicago and the University of Houston proposes a solution.

They show how rainwater could have helped create a meshy wall around protocells 3.8 billion years ago, a critical step in the transition from tiny beads of RNA to every bacterium, plant, animal, and human that ever lived.

The paper was published Aug. 21 in Science Advances by UChicago Pritzker Molecular Engineering (PME) postdoctoral researcher Aman Agrawal and his co-authors—including PME Dean Emeritus Matthew Tirrell and Nobel Prize-winning biologist Jack Szostak, director of UChicago’s Chicago Center for the Origins of Life.

“This is a distinctive and novel observation,” said Tirrell.

Droplets and discovery

The research looks at “coacervate droplets”—naturally occurring compartments of complex molecules like proteins, lipids, and RNA. (In the early 2000s, Szostak started looking at RNA as the first biological material to develop, rather than DNA.)

The droplets, which behave like drops of cooking oil in water, have long been eyed as a candidate for the first protocells. But there was a problem, Szostak found in 2014.

It wasn’t that these droplets couldn’t exchange molecules between each other, a key step in evolution; the problem was that they did it too well, and too fast. Any droplet containing a new, potentially useful pre-life mutation of RNA would exchange this RNA with the other RNA droplets within minutes, meaning they would quickly all be the same.

There would be no differentiation and no competition—meaning no evolution. And that means no life.

“If molecules continually exchange between droplets or between cells, then all the cells after a short while will look alike, and there will be no evolution because you are ending up with identical clones,” Agrawal said.

Agrawal started transferring coacervate droplets into distilled water during his PhD research at the University of Houston with Prof. Alamgir Karim, studying their behavior under an electric field. At this point, the research had nothing to do with the origin of life—just studying the fascinating material from an engineering perspective.

Karim had worked decades earlier at the University of Minnesota under one of the world’s top experts—Tirrell, who later became founding dean of the UChicago Pritzker School of Molecular Engineering. During a lunch with Agrawal and Karim, Tirrell brought up how the research into the effects of distilled water on coacervate droplets might relate to the origin of life on Earth. Tirrell asked where distilled water would have existed 3.8 billion years ago.

“I spontaneously said ‘rainwater!’ His eyes lit up and he was very excited at the suggestion,” Karim said. “So, you can say it was a spontaneous combustion of ideas or ideation!”

Tirrell brought Agrawal’s distilled water research to Szostak, who had recently joined the University of Chicago to lead a new push to understand the origins of life on Earth.

Working with RNA samples from Szostak, Agrawal found that transferring coacervate droplets into distilled water increased the time scale of RNA exchange – from mere minutes to several days. This was long enough for mutation, competition, and evolution.

Then, to make sure rain itself could work rather than distilled water, “We simply collected water from rain in Houston and tested the stability of our droplets in it, just to make sure what we are reporting is accurate,” Agrawal said.

In tests with the actual rainwater and with lab water modified to mimic the acidity of rainwater, they found the same results. The meshy walls formed, creating the conditions that could have led to life.

The chemical composition of the rain falling over Houston in the 2020s is not the rain that would have fallen 750 million years after the Earth formed, and the same can be said for the model protocell system Agrawal tested. The new paper proves that this approach of building a meshy wall around protocells is possible and can work together to compartmentalize the molecules of life, putting researchers closer than ever to finding the right set of chemical and environmental conditions that allow protocells to evolve.

“The molecules we used to build these protocells are just models until more suitable molecules can be found as substitutes,” Agrawal said. “While the chemistry would be a little bit different, the physics will remain the same.”

Interdisciplinary findings

Life is by nature interdisciplinary, so Szostak, the director of UChicago’s Chicago Center for the Origins of Life, said it was natural to collaborate with both UChicago PME, UChicago’s interdisciplinary school of molecular engineering, and the chemical engineering department at the University of Houston.

“Engineers have been studying the physical chemistry of these types of complexes—and polymer chemistry more generally—for a long time. It makes sense that there's expertise in the engineering school,” Szostak said. “When we're looking at something like the origin of life, it's so complicated and there are so many parts that we need people to get involved who have any kind of relevant experience.”

Citation: “Did the exposure of coacervate droplets to rain make them the first stable protocells?” Agrawal et al, Science Advances, August 21, 2024. DOI: 10.1126/sciadv.adn9657

Funding: Houston Endowment Fellowship, Welch Foundation, U.S. Department of Energy

—Adapted from an article published by the Pritzker School of Molecular Engineering.