Jerusalem, 30 September, 2025 (TPS-IL) — For decades, scientists have wondered why life settled on just 20 amino acids when many other types were available on early Earth. An Israeli study released on Monday suggests it wasn’t random: the stability of molecular assemblies likely gave “alpha amino acids” an evolutionary edge, providing a testable reason for a long-standing question in origins-of-life research.
The research, led by Dr. Moran Frenkel-Pinter of the Hebrew University of Jerusalem, indicates that the answer lies not just in chemistry but in the stability of early molecular assemblies, offering fresh insight into how life chose its building blocks.
Frenkel-Pinter and her team, including Ms. Sarah Fisher and Mr. Yishi Ezerzer, studied depsipeptides — simple, peptide-like molecules thought to form naturally on the early Earth. Unlike modern peptides, depsipeptides contain a mix of ester and amide bonds, making them easier to form under prebiotic conditions but less stable over time. The researchers wanted to know why alpha amino acids were favored over other abundant prebiotic options like beta or gamma amino acids.
To find out, the team synthesized depsipeptides using a variety of hydroxy and amino acids and observed how they self-assembled. The results were striking. Depsipeptides built from alpha amino acids formed droplet-like assemblies that remained stable for weeks, even after repeated freezing and thawing. Beta-based assemblies, in contrast, were far less stable and often separated in solution.
“Self-assembly is one of life’s most fundamental prerequisites,” Dr. Frenkel-Pinter said. “Our findings suggest that the superior ability of alpha-based proto-peptides to form stable compartments may have given them a crucial evolutionary edge, setting the stage for the protein backbones we see in biology today.”
For the student researchers, the discovery is both a scientific and personal milestone. “The question of why evolution handpicked a specific set of amino acids has remained a mystery for a very long time,” said Yishi Ezerzer, a master’s student co-leading the project. “Taking even a single step toward answering this long-lasting question is remarkable, and it is a privilege to contribute to this pursuit.”
Sarah Fisher stressed the broader significance of the findings. “We demonstrate here, for the first time, the ability of depsipeptides to self-assemble, similar to modern peptides. While these findings are a breakthrough in chemical evolution, they may also inform fields such as pharmaceuticals, where designing stable peptide structures is key,” she said.
By directly comparing alpha and beta proto-peptide backbones, the study proposes an assembly-driven model for the origins of life. It suggests that the choice of alpha amino acids was not just a matter of chemical availability, but of functional advantage: molecules that could form long-lasting, compartment-like structures were more likely to survive and evolve.
Beyond the origins-of-life question, understanding these molecular principles could guide modern synthetic biology, drug design, and nanotechnology.
The study was published in the peer-reviewed journal Proceedings of the National Academy of Sciences.
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