New studies indicate that rainwater might have played a role in forming a protective mesh around protocells about 3.8 billion years ago, which was a crucial development in evolving from simple RNA beads to complex forms of life including bacteria, plants, animals, and humans.
A significant unresolved issue regarding the origin of life is understanding how RNA droplets found in the primordial soup evolved into the membrane-secured structures we identify 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 published a paper proposing a potential solution.
In an article released today in Science Advances, UChicago PME postdoctoral researcher Aman Agrawal, along with his colleagues, including decorated researcher Matthew Tirrell and Nobel Prize-winning scientist Jack Szostak, outlines how rainwater could have contributed to the formation of a protective mesh around protocells 3.8 billion years ago. This was a vital step in the evolution from tiny RNA beads to every form of life.
“This is a unique and insightful finding,” remarked Tirrell.
The research focuses on “coacervate droplets”, which are natural clusters of complex molecules like proteins, lipids, and RNA. These droplets behave similarly to oil droplets in water and have been considered promising candidates for the first protocells. However, there was a challenge. The issue was not that these droplets couldn’t exchange molecules—a key evolutionary step—but rather that they did so excessively and too quickly.
Whenever a droplet held a new, potentially beneficial mutation of RNA, it would rapidly share this RNA with other droplets, resulting in all of them becoming identical within minutes. This lack of differentiation and competition hindered any possibility of evolution, which means life itself would not emerge.
“If molecules are constantly swapping between droplets or cells, all cells will quickly become identical, eliminating the chance for evolution since you’d only have clones,” Agrawal explained.
Engineering a Solution
Life inherently intersects various scientific fields, so Szostak, who directs UChicago’s Chicago Center for the Origins of Life, saw the value in collaborating with both UChicago PME and the University of Houston’s Chemical Engineering Department.
“Engineers have been exploring the physical and chemical properties of these complexes—and polymer chemistry in general—for a substantial time,” Szostak noted. “For studies on the origin of life, the complexity and multitude of parts call for input from anyone with relevant expertise.”
In the early 2000s, Szostak began to investigate RNA as the earliest biological substance, solving a longstanding dilemma for researchers focused on DNA and proteins as origins of life.
“It’s a classic chicken-egg scenario. Which came first?” Agrawal remarked. “DNA encodes information but can’t perform functions, whereas proteins execute functionalities but lack the means to carry heritable information.”
Researchers such as Szostak posited that RNA likely emerged first, managing all essential tasks, with proteins and DNA evolving later.”
“RNA is a molecule capable of encoding information like DNA, but also folding like proteins, allowing it to perform various functions such as catalysis,” Agrawal explained.
RNA was seen as a prime candidate among early biological materials. Coacervate droplets similarly stood as the earliest protocell contenders, particularly those containing initial forms of RNA.
However, Szostak challenged this notion in 2014 by revealing that RNA within coacervate droplets exchanged too rapidly to maintain distinct identities.
“You can create a variety of coacervate droplet types, but they won’t preserve their uniqueness as they quickly swap RNA content. This has been a persistent issue,” Szostak stated. “Our latest research demonstrates that we can mitigate some of this problem by placing these coacervate droplets in distilled water—like rainwater or any freshwater—allowing them to develop a resilient outer layer that limits RNA exchange.”
‘A Spontaneous Combustion of Ideas’
During his PhD at the University of Houston, Agrawal began transferring coacervate droplets into distilled water while examining their behavior under electric fields, although the origin of life was not the focus then.
“Chemical and materials engineers are skilled in manipulating material properties like interfacial tension, the influence of charged polymers, and controls on salt and pH,” noted Alamgir Karim, Agrawal’s former advisor and senior co-author of the paper. “These factors are essential in studies of ‘complex fluids’—similar to shampoo and liquid soap.”
Agrawal aimed to explore various fundamental properties of coacervates during his doctoral studies. While this was outside of Karim’s area, Karim had previously worked with Tirrell, an expert in the field, at the University of Minnesota.
Over lunch with Agrawal and Karim, Tirrell mentioned how distilled water’s effects on coacervate droplets might relate to life’s beginnings on Earth. Tirrell inquired where distilled water might have existed 3.8 billion years ago.
“I immediately suggested ‘rainwater!’ His face lit up with excitement,” Karim recounted. “One could describe it as a spontaneous combustion of ideas!”
Tirrell then shared Agrawal’s findings about distilled water with Szostak, who had recently joined UChicago to spearhead the Origins of Life Initiative, asking the same question he had posed to Karim.
“I asked him, ‘Where could distilled water come from in a prebiotic environment?'” Tirrell recalled. “Jack responded just as I had hoped—he said rain.”
Utilizing RNA samples provided by Szostak, Agrawal discovered that immersing coacervate droplets in distilled water significantly extended the time required for RNA to be exchanged—from mere minutes to several days. This expanded timeframe allowed for mutation, competition, and ultimately evolution to occur.
“If you have unstable protocell populations, they will exchange genetic material and become clones, preventing any Darwinian evolution,” Agrawal elaborated. “However, if they stabilize against excessive exchange, maintaining genetic information for several days allows mutations in the genetic sequences, enabling the population to evolve.”
Rain, Checked
Initially, Agrawal conducted experiments using deionized water, filtered in laboratory conditions. “This raised questions among journal reviewers about the impact of potentially acidic prebiotic rainwater,” he mentioned.
Commercial laboratory water is devoid of contaminants, salt, and maintains a perfectly neutral pH, which is not representative of real-world conditions. Thus, researchers needed something that closely resembled genuine rain.
So, what could better reflect rain than actual rain?
“We simply collected rainwater from Houston and evaluated the stability of our droplets in it, ensuring our findings were valid,” Agrawal said.
Tests using both natural rainwater and lab water adjusted to mimic rainwater’s acidity yielded consistent results. The formation of protective meshy walls created conditions that might have been conducive to the origins of life.
It’s essential to recognize that the chemical makeup of rain in Houston today differs from that of rain approximately 750 million years after Earth’s formation, just as variations exist in the model protocell systems Agrawal examined. The findings in the new paper demonstrate that this technique for establishing a protective mesh around protocells is feasible and could compartmentalize essential molecules of life, propelling researchers closer to identifying the right chemical and environmental conditions that would allow protocells to evolve.
“The molecules used to create these protocells are merely models until we can discover more appropriate substitutes,” Agrawal clarified. “While the chemistry may differ slightly, the underlying physics remain the same.”