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Where Did We Come From? Answering the Century-Old Question on the Origins of Life

The mysteries of life may not be hidden in an undiscovered fossil, but a tiny, self-replicating globule called a coacervate droplet.

First proposed in the 1920s, chemical evolution suggests that life began from simple, small molecules that accumulated to become macromolecules, which then evolved to form proliferative molecular assemblies. Following this theory, many scientists proceeded to conduct studies to experimentally verify the RNA world hypothesis, where only self-replicating genetic material existed prior to the evolution of DNA and proteins.

“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,” explained Muneyuki Matsuo, an assistant professor of chemistry in the Graduate School of Integrated Sciences for Life at Hiroshima University. The hypothesis has remained largely unverified due to experimental constraints. Scientists could not replicate the proliferating prebiotic system to simulate the emergence of life since different conditions are required for polymer generation and self-assembly, leaving them wondering how free-form chemicals of early Earth eventually became life.

To answer this century-old question, Matsuo partnered with Kensuke Kurihara, a researcher at KYOCERA Corporation, to uncover the missing link between chemistry and biology in the origins of life. Inspired by de Duve’s “thioester world” hypothesis, which argues that prebiotic peptides might have been generated from amino acid thioesters under mild, aqueous conditions, the team constructed autocatalytic self-proliferating peptide droplets that are expected to provide valuable clues to explain the emergence of the first living organisms on primordial Earth.

Like many researchers, both Matsuo and Kurihara initially thought that environment was the primary factor that allowed life to emerge. The ingredients of life must have formed under high pressure and temperature before cooling down to more life-friendly conditions. However, “Proliferation requires spontaneous polymer production and self-assembly under the same conditions,” said Matsuo, highlighting the issue of propagation. Therefore, the team sought to investigate the conditions suitable for concurrent peptide generation and self-assembly.

The scientists designed and synthesised a new probiotic monomer from amino acid derivatives as a precursor to the self-assembly of primitive cells. When added to room temperature water at atmospheric pressure, it was found that the amino acid derivatives condensed and arranged into peptides which then spontaneously formed droplets. As they fed the mixture with more amino acids, the droplets grew in both number and size.

When the team enriched the droplets with nucleic acids and lipids, the researchers discovered that the droplets were more likely to survive against external stimuli. In particular, the droplets were able to resist dissolution by lipids and maintained themselves if the concentrated nucleic acids were localised at the inner boundary of the droplet.

“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 said. “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.”

With these findings, the researchers are optimistic that their study can provide experimental constructs for origins-of-life research and open a new door in the development of peptide-based materials. Currently, the team is planning 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. [APBN]

Source: Matsuo et al. (2021). Proliferating coacervate droplets as the missing link between chemistry and biology in the origins of life. Nature Communications, 12, 5487.