Investigating how life arose on such a distant early Earth is one of science’s most fascinating challenges. Under what conditions must the building blocks of more complex life form? One of the main answers is based on the so-called RNA world concept, which was proposed by molecular biology pioneer Walter Gilbert in 1986. According to this hypothesis, nucleotides are produced from the “primordial soup” and short RNA molecules are produced from nucleotides. These so-called oligonucleotides are already able to encode small amounts of genetic information.
Since such single-stranded RNA molecules can also bind into double strands, however, this creates the theoretical prospect that these molecules can replicate themselves. In each case only two nucleotides are bound together, which means that one strand is the exact counterpart of the other strand, thus forming a template for the other strand.
Over the course of evolution, this duplication may improve and give rise to more complex life at some point. Thomas Carell, a chemist at the University of Munich, said: “The idea of the RNA world has a great advantage in that it outlines a pathway through which complex biological macromolecules, such as nucleic acids with optimised catalysis and at the same time information-coding properties, can emerge.” As we understand it today, genetic material is made up of double-stranded DNA, a slightly modified, durable form of macromolecules composed of nucleotides.”
However, this hypothesis is not without problems. For example, RNS is a very fragile molecule, especially when it gets long. Furthermore, it is unclear how the connection between RNA molecules and the protein world arises, for which genetic material, as we know it, provides the blueprint. As described in a new paper published in the journal Nature, Carell’s team has discovered a way in which this connection might occur.
RNA itself is a complex macromolecule. In addition to the four canonical bases A, C, G and U, which encode genetic information, it also contains non-canonical bases, some of which have very different structures. These non-information-encoding nucleotides are important for the functioning of RNA molecules. Researchers now have more than 120 of these modified RNA nucleosides, which nature incorporates into RNA molecules. They are most likely leftovers from the previous RNA world.
Carell’s group has now discovered that these non-canonical nucleosides are the key ingredients, just like it, that connect the RNA world with the protein world. According to Carell, some of these molecular fossils, when located in RNA, can “decorate” themselves with single amino acids or even small chains of amino acids (peptides). This results in small chimeric RNA-peptide structures when an amino acid or peptide happens to be present in a solution at the same time as the RNA. In such structures, the amino acids and peptides attached to the RNA then even react with each other, forming larger and more complex peptides. “In this way, we have created RNA-peptide particles in the laboratory that can encode genetic information and even form elongated peptides,” Carell said.
Thus, ancient fossil nucleosides are somewhat similar to the nucleus in RNA, forming a core upon which long peptide chains can grow. On some strands of RNA, the peptide even grew at several points. “That was a very surprising finding,” Carell said. “It is possible that there never was a pure RNA world, but RNA and peptides coexisted in a common molecule from the beginning. Therefore, we should expand the concept of the RNA world to that of the RNA-peptide world. Peptides and RNAs in their Mutual support during evolution, new ideas come up.”
According to the new theory, a decisive factor at the outset was the presence of RNA molecules, which could “decorate” themselves with amino acids and peptides, linking them into larger peptide structures. “RNA slowly develops into an ever-improving catalyst for amino acid linkages,” Carell said. This relationship between RNA and peptides or proteins has been maintained to this day. The most important RNA catalyst is the ribosome, which still links amino acids into long peptide chains today. As one of the most complex RNA machines, it is responsible for translating genetic information into functional proteins in every cell. “So, the RNA-peptide world solves the chicken-and-egg problem,” Carell said. “This new idea creates a foundation on which the origin of life gradually becomes explainable.”