The missing link that helps to explain the origins of life may not be an as-yet-undiscovered fossil, but rather, could be embodied in a tiny, self-replicating globule called a coacervate droplet, which researchers in Japan have developed to represent the evolution of chemistry into biology.
“Chemical evolution was first proposed in the 1920s as the idea that life first originated with the formation of macromolecules from simple small molecules, and those macromolecules formed molecular assemblies that could proliferate,” said first-author Muneyuki Matsuo, PhD, assistant professor of chemistry in the Graduate School of Integrated Sciences for Life at Hiroshima University. “Since then, many studies have been conducted to verify the RNA world hypothesis—where only self-replicating genetic material existed prior to the evolution of DNA and proteins—experimentally. However, the origin of molecular assemblies that proliferate from small molecules has remained a mystery for about a hundred years since the advent of the chemical evolution scenario. It has been the missing link between chemistry and biology in the origin of life.”
Matsuo and Kensuke Kurihara, PhD, a researcher at Kyocera, report in Nature Communications on the development of their proliferating peptide-based droplets, in a paper titled, “Proliferating coacervate droplets as the missing link between chemistry and biology in the origins of life,” in which they concluded, “This study may serve to explain the emergence of the first living organisms on primordial Earth.”
Matsuo and Kurihara set out to answer the century-old question: how did the free-form chemicals of early Earth become life? Like many researchers, they initially thought it came down to the environment, such that the ingredients formed under high pressure and temperature, then cooled into more life-friendly conditions. “The hypothesis that prebiotic molecules were transformed into polymers that evolved into proliferating molecular assemblages and eventually a primitive cell was first proposed about 100 years ago,” the scientists wrote in their paper. But the issue remained propagation. “Proliferation requires spontaneous polymer production and self-assembly under the same conditions,” Matsuo said. And as the published report continued, “to the best of our knowledge … no model of a proliferating prebiotic system has yet been realized because different conditions are required for polymer generation and self-assembly.”
The researchers described how they designed and synthesized a prebiotic monomer from amino acid derivatives, as a precursor to the self-assembly of primitive cells. When added to room temperature water at atmospheric pressure, the amino acid derivatives condensed, arranging into peptides, which then spontaneously formed droplets. The droplets grew in size and in number when fed with more amino acids. “ … we identify conditions suitable for concurrent peptide generation and self-assembly, and we show how a proliferating peptide-based droplet could be created by using synthesized amino acid thioesters as prebiotic monomers,” they wrote. “Oligopeptides generated from the monomers spontaneously formed droplets through liquid–liquid phase separation in water. The droplets underwent a steady growth–division cycle by periodic addition of monomers through autocatalytic self-reproduction.”
Importantly, the researchers found that the droplets could concentrate nucleic acids, and they were more likely to survive against external stimuli if they exhibited this function. “A droplet-based protocell could have served as a link between ‘chemistry’ and ‘biology’ during the origins of life,” Matsuo noted. “This study may serve to explain the emergence of the first living organisms on primordial Earth.”
And by constructing peptide droplets that proliferate with feeding on novel amino acid derivatives, “we have experimentally elucidated the long-standing mystery of how prebiotic ancestors were able to proliferate and survive by selectively concentrating prebiotic chemicals,” Matsuo continued. “Rather than an RNA world, we found that ‘droplet world’ may be a more accurate description, as our results suggest that droplets became evolvable molecular aggregates—one of which became our common ancestor.”
The researchers concluded in their paper, “… these proliferating droplets composed of peptides could have served as containers to integrate RNA, lipids, and peptides during the early history of Earth because the droplets not only incorporated nucleic acids and lipids but also acquired the ability to survive by accelerating interactions among these constituents … In summary, because the process of evolution from amino acid thioesters to primitive living things could be realized by the concentration of RNA, lipids, and peptides inside a proliferating droplet and a subsequent expression of a biological-like function, it seems appropriate to call this scenario the ‘droplet world hypothesis’.”
The researchers plan to continue investigating the process of evolution from amino acid derivatives to primitive living cells, as well as improve their platform to verify and study the origins of life and continued evolution.