Translartion. Region: Russians Fedetion –
Source: State University Higher School of Economics – State University Higher School of Economics –
Scientific consultant International Bioinformatics Laboratory HSE University’s Alan Herbert has proposed a new explanation for one of the unsolved mysteries of biology – the origin of the genetic code. According to a study published in the journalBiology Letters, the modern genetic code could have emerged thanks to self-organizing molecular complexes – tinkers. The author put forward a new hypothesis based on the analysis of secondary DNA structures using the AlphaFold3 neural network.
The genetic code is the “alphabet” that underlies the functioning of any living system on Earth. It determines what is written in the “instructions” for the organism and how it should be read. The modern genetic code consists of codons, each of which contains three nucleotides. These triplets code for amino acids, which then participate in the synthesis of proteins. Scientists have been studying the genetic code for over 70 years, but one of the most important questions – how exactly it arose – has not yet received a clear answer.
Scientific consultant of the International Laboratory of Bioinformatics of the National Research University Higher School of Economics, Professor Alan Herbert, proposed a new explanation for the origin of the code. In his opinion, during the course of evolution, flipons — special sections of DNA capable of forming secondary structures — played a key role in the formation of the modern genetic code.
The classic DNA molecule, described by Francis Crick and James Watson, is a double helix twisted to the right. But scientists have discovered that there are alternative DNA structures: Z-DNA twisted to the left; three-stranded and four-stranded sequences; and DNA with a cross-shaped structure – i-motifs. These unusual structures arise under certain physiological conditions, and their type depends on the set and order of nucleotides in the flipon itself. The simplest flipons are formed from simple nucleotide repeats, so it is assumed that there were enough of them in the so-called primordial soup.
Using a neural network Alfafold3 DeepMind’s Alan Herbert analyzed the nature of the bonds between flipons and amino acids. “It turned out that flipons formed from two-letter repeats bind very well to simple peptides consisting of two-letter amino acid repeats. And this is exactly the kind of correspondence that is present in the modern genetic code,” comments Maria Poptsova, head of the International Bioinformatics Laboratory at the National Research University Higher School of Economics.
For example, the cytosine-guanine repeat CGCGCG forms Z-DNA. A peptide with an arginine-alanine repeat RARARA binds very well to such a sequence. In the modern code, arginine corresponds to the codon CGC, and alanine to GCG. If we examine the structure of spatial interactions in detail, the best connection is obtained from non-overlapping triplets: CGCGCG binds to RA.
In the publication, Alan Herbert reviews dozens of examples of interactions between short repeat flipons and amino acid repeat peptides. It turns out that reactions leading to mutual chain elongation can also occur, especially in the presence of magnesium and zinc. These metals serve as catalysts for such reactions.
According to the author of the study, such complexes were once formed thanks to special components – tinkers, the so-called artisans of nature, as Francois Jacob called them. In the work of Professor Herbert, such self-reproducing artisans are structures consisting of flipons and peptides. Tinkers used DNA as a matrix for protein synthesis, and proteins, in turn, contributed to the elongation of the DNA helix. As a result, a triplet non-overlapping code arose: an odd number of bases allows encoding sequences of different amino acids, and the nature of the connections between flipons and amino acids requires that each codon correspond to only one amino acid.
“The role of flipons as tinkers in the initial biological evolution is a fundamentally new view of the origin of life. It is no exaggeration to say that if the theory is confirmed experimentally, our colleague Dr. Herbert deserves the Nobel Prize,” says Maria Poptsova. “The discovery of the interactions of flipons with amino acids in accordance with the table of the modern genetic code proves that the emergence of the genetic code is not an accident, but a natural result of evolution. Nature does not invent anything from scratch, it comes up with new mechanisms from what is available. Nature acts like a careless craftsman who, when he needs to quickly make something that works, not necessarily reliable and durable, grabs whatever comes to hand. This is the property behind the concept of “tinker.”
“In general, the proposed scheme does not require DNA, RNA, or the peptide world to explain the origin of life,” writes Alan Herbert in his paper. “Instead, the tinkers described are the agents that facilitate this possibility. They arise from a simple match between low-complexity nucleotides and simple peptide polymers, using metals to catalyze their initial replication. By feeding the prebiotic soup copies of themselves, these tinkers quite naturally evolved a non-overlapping, triplet genetic code.”
Beyond understanding the origins of life, studying tinkers could lead to new technologies, including artificial self-organizing systems and self-healing materials. The ability of tinkers to combine different chemical elements could be used to direct the evolution of new biomolecules.
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