At the heart of the search for the origins of life lies a deep mystery: how did simple RNA droplets in the primordial soup evolve into the complex, membrane-bound cells that underlie all life forms? A groundbreaking paper by a team of engineers from the Universities of Houston and Chicago presents a fascinating solution to this age-old puzzle.
This suggests that rainwater may have played a crucial role in forming a porous barrier around protocells 3.8 billion years ago, marking a crucial milestone in the transition from simple RNA structures to the diverse range of life forms that inhabit our planet today.
“Although it is impossible to know the exact conditions on early Earth, our experiments show that this pathway to stabilizing protocells may have been a crucial step in enabling the evolution of these protocells,” said Alamgir Karim of UH.
The research delves into the fascinating world of “coacervate droplets” – natural compartments composed of complex molecules such as proteins, lipids and RNA. These droplets, which resemble drops of cooking oil in water, have long been considered prime candidates for the first protocells.
There’s a catch, though. The problem isn’t the inability of these droplets to exchange molecules – a crucial aspect of evolution. Rather, the problem lies in the uncanny efficiency and speed with which they do so.
Any droplet containing a novel, potentially advantageous RNA mutation from before life would rapidly exchange this genetic material with other RNA droplets, leading to rapid homogenization. This homogeneity hinders differentiation and competition, essential components of evolution. Without them, no life can thrive.
“If molecules are constantly exchanged between droplets or between cells, all cells will soon look the same and there will be no evolution because you end up with identical clones,” said former UH doctoral student Aman Agrawal (now a postdoctoral fellow at UChicago).
In the early 2000s, Szostak began studying RNA as the first biological material to evolve, addressing a problem that had long puzzled researchers who considered DNA or proteins to be the earliest molecules of life.
“It’s like the chicken and egg problem. Which came first?” Said Agrawal. “DNA is the molecule that encodes information but cannot perform a function. Proteins are the molecules that perform functions but do not encode heritable information.”
Szostak and other researchers suspected that RNA was the first actor, essentially “take care of everything”, to use Agrawal’s words, gradually evolving into proteins and DNA.
“RNA is a molecule that can encode information like DNA, but also folds like proteins, so it can also perform functions such as catalysis,” Said Agrawal.
RNA emerged as a strong candidate for the first biological material, while coacervate droplets seemed to be promising candidates for the first protocells. These droplets, containing primitive forms of RNA, seemed to be the natural progression.
That is, until Szostak challenged this theory and dampened the enthusiasm by publishing a paper in 2014 revealing that RNA exchange in coacervate droplets occurred too quickly.
“You can make all kinds of droplets from different types of coacervate, but they don’t retain their own identity. They tend to exchange their RNA content too quickly. This has been a problem for a long time,” said Szostak. “What we show in this new paper is that you can overcome at least part of this problem by transferring these coacervate droplets into distilled water – for example rainwater or fresh water of any kind – and they form a kind of hard skin around the droplets that prevents them from exchanging RNA contents.”
During his PhD at the University of Houston, Agrawal embarked on a fascinating journey by transferring coacervate droplets into distilled water and observing their behavior in an electric field. In this initial phase, the research focused solely on studying the material from an engineering perspective, with no reference to the origin of life.
Professor Alamgir Karim, Agrawal’s former doctoral supervisor at the University of Houston and lead co-author of the new paper, emphasized the importance of engineers, particularly those specializing in chemistry and materials, in understanding the manipulation of material properties such as interfacial tension, the role of charged polymers, salt, pH control and other crucial aspects of “complex fluids” – drawing parallels to everyday products such as shampoo and liquid soap.
Although coacervates are not Karim’s primary area of study, his previous experience at the University of Minnesota under the guidance of one of the world’s leading experts, Tirrell, who later became the founding dean of the UChicago Pritzker School of Molecular Engineering, provided him with invaluable insights.
Over lunch with Agrawal and Karim, Tirrell brought a new perspective to the table. He asked how studying the effects of distilled water on coacervate droplets might reveal connections to the origin of life on Earth, which suggested that distilled water existed 3.8 billion years ago.
Szostak and Agrawal’s work found that transferring coacervate droplets to distilled water extended the time frame of RNA exchange, making mutation and evolution possible. Agrawal emphasized the importance of population stability for evolution. The transition from using deionized water to using acidic prebiotic rainwater was a significant turning point in the experiments. Working with material that resembles real rainwater is crucial for accurate results.
“We simply collected rainwater from Houston and tested the stability of our drops in it, just to make sure that what we are reporting is correct,” said Agrawal. Agrawal and fellow student Anusha Vonteddu grabbed a few beakers from Karim’s lab during a downpour to collect some rainwater right outside the Agrawal Engineering Research Building.
“Agrawal and Vonteddu wanted to use their rain samples in cups to prove our main hypothesis that rainwater could have stabilized the protocells on the early Earth,” said Karim.
In groundbreaking experiments with real rainwater and water altered in the laboratory to mimic the acidity of rainwater, researchers observed a remarkable result: the formation of web-like walls that may have provided the perfect conditions for the emergence of life. “This discovery has the potential to revolutionize our understanding of prebiotic life,” said Karim, one of the lead researchers.
It is important to note that the chemical composition of today’s rain in Houston is very different from the rain that fell 750 million years after the Earth was formed. Likewise, the model protocell system tested by Agrawal cannot exactly reproduce the conditions at that time.
Still, the findings from the new study clearly demonstrate that it is possible to construct web-like walls around protocells, and how these structures can effectively compartmentalize the building blocks of life. This brings us closer than ever to discovering the specific chemical and environmental conditions that may have enabled protocell evolution.
“The molecules we used to build these protocells are only models until more suitable molecules can be found as replacements,” Said Agrawal. “Even if the chemistry were a little different, the physics would remain the same.”
Journal reference:
- Aman Agrawal, Aleksandar Radakovic, Anusha Vonteddu, Syed Rizvi, Vivian N. Huynh, Jack F. Douglas, Matthew V. Tirrell, Alamgir Karim, Jack W. Szostak. Did rain-induced coacervate droplets become the first stable protocells? Science Advances, 2024; DOI: 10.1126/sciadv.adn9657
