[Nov 11, 2022: Norifumi Miyokawa, Hiroshima University]
A team of Japanese scientists found the missing link between chemistry and biology in the origins of life. (CREDIT: Getty Images)
The missing link isn’t a not-yet-discovered fossil, after all. It’s a tiny, self-replicating globule called a coacervate droplet, developed by two researchers in Japan to represent the evolution of chemistry into biology.
They published their results in Nature Communications.
“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, 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”, he continued.
Matsuo partnered with Kensuke Kurihara, researcher at KYOCERA Corporation, 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: the ingredients formed under high pressure and temperature, then cooled into more life-friendly conditions. The issue was propagation.
“Proliferation requires spontaneous polymer production and self-assembly under the same conditions,” Matsuo said.
They designed and synthesized a new 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.
A team of Japanese scientists found the missing link between chemistry and biology in the origins of life. (CREDIT: Hiroshima University)
The droplets grew in size and in number when fed with more amino acids. The researchers also found that the droplets could concentrate nucleic acids — genetic material — 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 said. “This study may serve to explain the emergence of the first living organisms on primordial Earth.”
In the first stage, the amino acid thioester is oligomerised to produce a peptide. Droplets are formed from the product by liquid−liquid phase separation (LLPS). Continuous addition of the amino acid thioesters as a source of nutrition and physical stimulus to the droplets allows the droplets to divide while they self-reproducing autocatalytically through the incorporation of nutrients. The robustness of the proliferating droplet reflects its ability to concentrate macromolecules such as nucleic acids. (CREDIT: Nature Communications)
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.
Because the process of evolution from amino acid thioesters to primitive living things could be realised 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”.
Various life-like functions can be imparted to a droplet by inserting alternative amino acids or peptides between cysteine and the thioester moiety in the current monomer or by using other alkylthiols as leaving groups. Interestingly, non-ribosomal peptide synthesis using a similar mechanism has been discovered in some bacteria and eukaryotic cells.
In these in vivo peptide syntheses, amino acid thioesters function as monomers to form peptides. Droplets that are composed of peptides and nucleic acids and that are formed inside a cell can serve as sites of reactions related to gene expression in modern cells.
These results are consistent with the scenario that the protocell was based on CDs formed by thioester reactions. Furthermore, because the droplet world hypothesis was derived from model experiments, a corollary of the hypothesis is that a protocell may have emerged by CiA-polymerisation of more primitive monomers than amino acid thioesters. The system proposed in this study is therefore a very powerful platform not only for verifying the ancient droplet world scenario of the origins of life but also for developing self-sustainable materials that mimic superior forms of life.
“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.”
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Note: Materials provided above by the Hiroshima University. Content may be edited for style and length.
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