Molecular cooperation at the threshold of life

Protein-like aggregates, called amyloids, can bind to molecules of genetic material. It is possible that these two types of molecules became stabilized during the development of life – and that this even paved the way for the genetic code.

How organisms develop from inanimate matter is one of the biggest questions in science. Although many possible explanations have been proposed, there are no definitive answers. This is not surprising: these processes took place 3 to 4 billion years ago, at a time when conditions on Earth were completely different from those of today.

Justify hypotheses with experimental data

“Over this vast period, evolution has completely erased traces of the origins of life,” says Roland Riek, professor of physical chemistry and associate director of the new Interdisciplinary Center for the Origin and Prevalence of Life. from ETH Zurich. Science has no choice but to formulate hypotheses and support them as thoroughly as possible with experimental data.

For years, Riek and his team have pursued the idea that protein-like aggregates, called amyloids, may have played an important role in the transition from chemistry to biology.

The first step for Riek’s research group was to demonstrate that such amyloids could form relatively easily under the conditions that probably prevailed on the early Earth: in the laboratory, all it takes is a little volcanic gas (as well as experimental skills and a lot of patience). ) so that simple amino acids combine into short peptide chains, which then spontaneously assemble into fibers.

Precursor molecules of life

Later, Riek’s team demonstrated that amyloids can replicate, meaning the molecules meet another decisive criterion to be considered precursor molecules of life. And now the researchers have taken the same line for the third time with their latest study, in which they show that amyloids are capable of binding to RNA and DNA molecules.

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

Increased stability as a major advantage

And yet, “Although we see differences in how RNA and DNA molecules bind to amyloids, we do not yet understand the significance of these differences,” says Riek. “Our model is probably still too simple.” This is why he considers another aspect of the results particularly important: when the genetic material attaches to the amyloids, both molecules gain stability. In ancient times, this increased stability may have proven to be a great advantage.

Indeed, at the time, in the so-called primordial soup, the biochemical molecules were very diluted. Compare this with today’s biological cells, in which these molecules are tightly packed together. “Amyloids have the proven potential to increase the local concentration and order of nucleotides in an otherwise dilute disordered system,” write the Riek researchers in their paper published in Journal of the American Chemical Society.

Riek points out that although competition is at the heart of Darwin’s theory of evolution, cooperation also played a major evolutionary role. Both classes of molecules benefit from the stabilizing interaction between amyloids and RNA or DNA molecules, because long-lived molecules accumulate more strongly over time than unstable substances. It may even be that molecular cooperation, rather than competition, was the decisive factor in the emergence of life.

“After all, there was probably no shortage of space or resources back then,” says Riek.