A recent study suggests that rainwater may have played a crucial role in the evolution of early RNA structures into protocells by forming protective barriers around them, facilitating their progression into more complex life forms.

A key question in the origin of life is how free-floating RNA molecules in the primordial soup transitioned into the membrane-bound structures that we now recognize as cells.

Researchers from the University of Chicago’s Pritzker School of Molecular Engineering (UChicago PME), the University of Houston’s Chemical Engineering Department, and the UChicago Chemistry Department have proposed a new explanation for this process.

In a study published in Science Advances, UChicago PME postdoctoral researcher Aman Agrawal, along with co-authors including UChicago PME Dean Emeritus Matthew Tirrell and Nobel laureate biologist Jack Szostak, reveal how rainwater could have created a protective mesh around protocells 3.8 billion years ago. This development was a critical step in the transformation from simple RNA droplets to the diversity of life forms that exist today.

“This is a unique and groundbreaking discovery,” Tirrell commented.

The Challenge of Protocell Stability

The research focuses on "coacervate droplets," which are naturally occurring compartments made of complex molecules such as proteins, lipids, and RNA. These droplets behave like oil in water and have long been considered potential candidates for the first protocells.

However, there was a significant challenge: these droplets exchanged molecules with one another too quickly.

If a droplet contained a new, potentially beneficial RNA mutation, it would quickly share this RNA with other droplets, leading to a lack of differentiation and competition—essential elements for evolution. Without these, life as we know it could not have emerged.

“If molecules continuously exchange between droplets or cells, eventually all cells will look alike, stalling evolution by producing identical clones,” Agrawal explained.

Collaborative Research and the Role of RNA

Given the complexity of life’s origins, Szostak, director of UChicago’s Chicago Center for the Origins of Life, saw the value in collaborating with UChicago PME and the University of Houston's Chemical Engineering Department.

“Engineers have extensive experience studying the physical chemistry of these complexes and polymer chemistry in general,” Szostak said. “When addressing something as intricate as the origin of life, involving experts from various fields is essential.”

In the early 2000s, Szostak began investigating RNA as the first biological material, addressing a long-standing issue that had puzzled researchers focusing on DNA or proteins as the earliest molecules of life.

“It’s a classic chicken-and-egg dilemma. Which came first?” Agrawal noted. “DNA encodes information but cannot perform functions, while proteins perform functions but don’t encode heritable information.”

Szostak and others proposed that RNA came first, handling both information storage and functional roles, with proteins and DNA evolving later.

“RNA, like DNA, can encode information, but it also folds like proteins, enabling it to perform catalytic functions,” Agrawal said.

RNA seemed a natural candidate for the first biological material, and coacervate droplets were likely candidates for the first protocells. The combination of early RNA and coacervate droplets appeared to be a logical next step.

Discovery of RNA Stability in Rainwater

Szostak's 2014 paper, however, presented a significant challenge to this theory by demonstrating that RNA in coacervate droplets exchanged too rapidly.

“You can create various types of coacervate droplets, but they don’t maintain their separate identities, exchanging RNA content too quickly. This has been a long-standing issue,” Szostak explained. “Our new study shows that this problem can be mitigated by transferring these droplets into distilled water—like rainwater—which forms a tough skin around the droplets, limiting RNA exchange.”

Bridging Engineering and Biology

Agrawal’s work with coacervate droplets and distilled water began during his PhD research at the University of Houston, where he studied their behavior under an electric field from an engineering perspective, with no initial connection to the origin of life.

“Engineers, particularly in Chemical and Materials fields, have deep knowledge of manipulating material properties like interfacial tension and the roles of charged polymers, salt, and pH,” said University of Houston Prof. Alamgir Karim, Agrawal’s former advisor and a senior co-author of the study. “These are all key aspects of ‘complex fluids’—think shampoo and liquid soap.”

Agrawal was interested in exploring fundamental properties of coacervates during his PhD, which led to a collaboration with Tirrell, who suggested the potential link between distilled water and the origin of life on Earth.

During a conversation with Karim and Agrawal, Tirrell speculated about where distilled water might have existed 3.8 billion years ago. “I spontaneously said, ‘rainwater!’ His eyes lit up with excitement,” Karim recalled. “It was a spontaneous combustion of ideas!”

Tirrell then introduced Agrawal’s research to Szostak, who had recently joined the University of Chicago. He posed the same question to Szostak, who responded with the expected answer: rain.

Implications for Prebiotic Evolution

Using RNA samples from Szostak, Agrawal found that transferring coacervate droplets into distilled water slowed RNA exchange from minutes to several days, allowing for mutation, competition, and evolution.

“If protocell populations are unstable, they exchange genetic material too quickly, becoming clones with no opportunity for Darwinian evolution,” Agrawal said. “But if they stabilize, allowing genetic mutations to occur over several days, a population can evolve.”

Initially, Agrawal used deionized water, which is purified in lab conditions. This prompted reviewers to question how prebiotic rainwater's acidity might affect the findings.

Real-World Testing and Future Directions

To address this, Agrawal collected rainwater in Houston and tested the stability of coacervate droplets. The results confirmed that meshy walls formed, creating conditions conducive to life.

While the chemical composition of modern rainwater differs from that of 3.8 billion years ago, the study demonstrates that building a meshy wall around protocells is possible, bringing researchers closer to understanding the right conditions for protocell evolution.

“The molecules used to create these protocells are just models until more suitable substitutes are found,” Agrawal said. “While the chemistry may vary, the physics remains the same.”

Sources:

Published 21 August 2024, Science Advances; “Did the exposure of coacervate droplets to rain make them the first stable protocells?”

DOI: 10.1126/sciadv.adn9657

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