The Amyloid Hypothesis: Rewriting the Origin of Life

New research examines how amyloids, which were able to form under early Earth conditions and bind to RNA and DNA, may have played a key role in the emergence of life by increasing molecular stability and promoting cooperation rather than competition.

The question of how living organisms emerged from inanimate matter remains one of the greatest mysteries of science. Despite numerous theories, a conclusive explanation is still unclear. This is hardly surprising considering that these events took place three to four billion years ago under completely different ancient conditions on Earth.

Justification of hypotheses with experimental data

“During this long period of time, evolution has thoroughly erased the traces leading to the origin of life,” says Roland Riek, Professor of Physical Chemistry and Deputy Director of the new interdisciplinary Center for the Origin and Prevalence of Life at ETH Zurich. Science has no choice but to formulate hypotheses – and to support them as comprehensively as possible with experimental data.

For years, Riek and his team have pursued the idea that protein-like aggregates, so-called amyloids, could have played an important role in the transition between chemistry and biology. The first step taken by Riek's research group was to show that such amyloids could form relatively easily under the conditions likely to have prevailed on the early Earth: in the laboratory, all it takes is a little volcanic gas (as well as experimental skill and a lot of patience). ) for easy amino acids combine to form short peptide chains, which then spontaneously assemble into fibers.

Precursor molecules of life

Riek's team later showed that amyloids can replicate themselves – meaning that the molecules meet another crucial criterion to be considered precursor molecules of life. And now the researchers are going in the same direction for a third time with their latest study, showing that amyloids are able to bind to molecules of both RNA And DNA.

These interactions are based in part on electrostatic attraction, as some amyloids are positively charged – at least in places – while the genetic material carries a negative charge, at least in a neutral to acidic environment. However, Riek and his team also found that the interactions also depend on the order of the RNA and DNA nucleotides in the genome. So they could represent a kind of precursor to the universal genetic code that unites all living things.

Increased stability is a big advantage

And yet: “We see differences in how the RNA and DNA molecules bind to the amyloids, but we do not yet understand what these differences mean,” says Riek. “Our model is probably still too simple.” He therefore sees another aspect of the results as particularly important: when the genetic material attaches to amyloids, both molecules gain stability. This increased stability may have proven to be a great advantage in ancient times.

Back then, in the so-called primordial soup, biochemical molecules were very diluted. Compare this to today's biological cells, where these molecules are packed tightly together. “Amyloids have been shown to have the potential to increase the local concentration and order of nucleotides in an otherwise dilute disordered system,” Riek’s researchers write in their recently published paper.

Riek points out that while competition is central to Darwin's theory of evolution, cooperation has also played an important role in evolution. Both classes of molecules benefit from the stabilizing interaction between amyloids and RNA or DNA molecules, since long-lived molecules accumulate more over time than unstable substances. It may even be that molecular cooperation, rather than competition, was the decisive factor in the emergence of life. “There was probably no shortage of space or resources back then,” says Riek.

Reference: “An Analysis of Nucleotide-Amyloid Interactions Reveals Selective Binding to Codon-Sized RNA” by Saroj K. Rout, Riccardo Cadalbert, Nina Schröder, Julia Wang, Johannes Zehnder, Olivia Gampp, Thomas Wiegand, Peter Güntert, David Klingler, Christoph Kreutz, Anna Knörlein, Jonathan Hall, Jason Greenwald and Roland Riek, October 2, 2023, Journal of the American Chemical Society.
DOI: 10.1021/jacs.3c06287