Scientists from the University of Cambridge have received new evidence in favor of the RNA world hypothesis. It turned out that small amino acid chains, when combined with RNA, improve their catalytic properties, allowing them to become less dependent on toxic ions. And this is a necessary condition for the formation of the first cells. "Lenta.ru" talks about the work published in the journal Nature.
According to the hypothesis of the RNA world, life arose from a simple biological system in which there was no DNA and protein molecules. It consisted of RNA complexes capable of not only storing genetic information, but also catalyzing chemical reactions (in this case, they were called ribozymes). In other words, they combined the functions of DNA and enzymes. Then the combination of RNA with peptides and deoxyribonucleic acid led to the emergence of unicellular organisms. However, the question arises: what was the benefit from the interaction between the RNA world and proteins?
Ribozymes, called RNA polymerases, are thought to have made up the bulk of the RNA world. They were replicators - objects capable of self-replication. The resources for this were nucleotides in the primary broth. In the beginning, ribozymes had a hard time copying themselves because their catalytic abilities were not developed. They made mistakes, which resulted in ribozymes with mutations. These changes could deprive RNA polymerase of the ability to catalyze; however, in some cases, this quality, on the contrary, improved. Over time, ribozymes reproduced faster and more accurately, became more numerous and won the competition for resources.
Thus, ribozymes were the primary genomes, since they stored genetic information about their own sequence. Later, they were encapsulated within particles formed by lipid membranes, which led to the formation of the first protocell. Scientists are able to synthesize analogs of the RNA polymerase ribozyme, which catalyze the synthesis of other ribozymes, or even copy short sequences of ribonucleotides. However, it is still not possible to obtain a ribozyme-replicator.
Ribosome Thermus thermophilus
Image: Public Domain / Wikimedia
There is another problem as well. The ribozymes synthesized in laboratories are active only at very high concentrations of magnesium ions, which destroy lipid membranes. This means that there is a fundamental incompatibility between ribonucleic RNA polymerases and the processes of protocell formation.
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The situation is saved by the fact that the RNA molecules have not been isolated from many other chemical compounds, such as peptides. Ribozymes could cooperate with amino acid sequences, which affected their function. This is also supported by the fact that the activity of ribozymes such as spliceosomes (cutting out introns from maturing messenger RNA), ribosomes (participating in protein synthesis) and ribonuclease P (catalyzing RNA degradation) depends on related proteins. Research has shown that certain proteins that bind to ribozymes cause changes in their secondary structure and function. Thus, in the case of ribonucleases P, proteins can reduce the concentration of magnesium ions necessary for their activity. With this in mind, the scientists decided to find out if peptides could affect the function of RNA polymerase ribozymes in a similar way, reducing their dependence on magnesium.
To answer this question, it is necessary to choose not any proteins, but only those that once interacted with ribozymes of the RNA world. Scientists turned to the structure of ribosomes, which are a kind of molecular relic. Research results indicate that ribosomes in their modern form were already present in LUCA - the common ancestor of all modern life forms.
The structure of the ribosome subunits of Thermus thermophilus
Image: Philipp Holliger / Cambridge
In the structure of the ribosome, formed by proteins, ribonucleic acids and ions, its evolution is recorded. Thus, the basis of the large ribosomal subunit is enriched with magnesium ions. Gradually, it was overgrown with additional modules in which ions were replaced by peptides. According to scientists, the relationship between ribozymes and amino acid chains reflects the evolutionary history of the RNA world and its transition to the RNA-peptide world. That is why the effect of peptides from ribosomes, which are considered the most ancient protein sequences on Earth, was analyzed.
The researchers identified multiple peptides from both ribosome subunits of the bacterium Thermus thermophilus, which enhanced the activity of the RNA polymerase Z ribozyme, which replicates RNA molecules.
Fluorescence microscopy image of membrane vesicles
Image: MRC Laboratory of Molecular Biology / Cambridge / United Kingdom
However, the most significant effect was possessed by the homopolymeric lysine decapeptide (K10), an amino acid sequence of ten lysine molecules. It supported ribozyme functions at low concentrations of magnesium ions, forming a peptide-ribozyme complex. Scientists have suggested that this is due to the stabilization of intermediates in the catalytic cycle.
To test if this peptide could promote the activity of ribozymes within the membrane compartment, the researchers conducted an experiment. Stable vesicles were obtained, consisting of phospholipids and diacylglycerols, inside which RNA was encapsulated. At a concentration of magnesium ions of 10 millimoles (safe for the membrane) and in the presence of K10, ribozyme-catalyzed RNA synthesis was observed. In the absence of magnesium, however, synthesis did not occur.
This indicates that the peptides did indeed allow ribozymes to carry out catalytic activity at low concentrations of toxic ions. As a result, the dependence of RNA polymerases on inorganic molecules decreased, which facilitated their evolution and, ultimately, the evolution of cells.
Alexander Enikeev
