The hidden mechanism of gene creation

Researchers at the University of Helsinki have discovered a mechanism that generates instantaneous birth DNA homologues, which may lead to the creation of new microRNA genes from non-coding DNA sequences. This discovery was made while studying DNA replication errors and their effect on it RNA Molecular structures, provides new insights into the origins of genes.

The complexity of living organisms is encoded within their genes, but where do these genes come from? Researchers at the University of Helsinki have resolved outstanding questions about the origin of small regulatory genes, and described the mechanism that creates their DNA homology. Under the right conditions, these homologs develop into microRNA genes.

Genes and proteins: the building blocks of life

The human genome contains ca. 20,000 genes are used to build proteins. The actions of these classical genes are coordinated by thousands of regulatory genes, the smallest of which encode microRNA molecules that are 22 base pairs in length. While the number of genes remains relatively constant, sometimes new genes appear during evolution. Like the origin of biological life, the origin of new genes continues to fascinate scientists.

Solve the alternating puzzle

All RNA molecules require alternating sets of bases that lock the molecule into its functional form. Importantly, the chances of random base mutations forming such progressively alternating pathways are very small, even for simple microRNA genes. Hence, the origin of these alternating sequences has puzzled researchers. Experts at the Institute of Biotechnology at the University of Helsinki in Finland have solved this puzzle, describing a mechanism that can instantly generate complete DNA homologues, thus creating new microRNA genes from previously non-coding DNA sequences.

Insights into DNA replication

In a project funded by the Academy of Finland, researchers studied errors in DNA replication. Ari Luitinoja, the project leader, compares DNA replication to printing text.

“DNA is copied one base at a time, and the mutations are usually single wrong bases, like errant strokes on a laptop keyboard. We studied a mechanism that leads to larger errors, like copying and pasting text from another context. We were interested Especially when you have copied the text backwards so that it creates symmetrical text.

Researchers studied the error mechanism in DNA replication and observed that some errors create homologs that can transform into hairpin structures. Credit: Ari Löytynoja

RNA structures and DNA errors.

Researchers have realized that DNA replication errors can sometimes be beneficial. They described these findings to Mikko Freelander, an expert in RNA biology. He immediately saw the connection to the structure of RNA molecules.

“In the RNA molecule, the bases of adjacent homologues can pair and form hairpin-like structures. Such structures are essential for the function of RNA molecules,” he explains.

The researchers decided to focus on microRNA genes because of their simple structure: The genes are very short—just a few dozen bases—and they have to fold into a hairpin structure to function properly.

The central idea was to model gene history using a custom computer algorithm. According to postdoctoral researcher Helle Monteinen, this allows the closest examination of the origin of genes to date.

“The complete genomes of dozens of primates and mammals are known. Comparison of their genomes reveals which ones Classify It possesses a palindrome pair of microRNA, which it lacks. “By detailed modeling of the history, we can see that complete homologs are created by single mutation events,” says Montinen.

The basic idea was to model gene history using information from related species. Modeling has shown that homologs of microRNA genes are generated by single mutation events. Credit: Ari Löytynoja

Archeology and cosmopolitanism

By focusing on humans and other primates, the researchers in Helsinki demonstrated that the newly discovered mechanism could explain at least a quarter of the new microRNA genes. Since similar cases have been found in other evolutionary lineages, the mechanism of origin seems universal.

In principle, the emergence of microRNA genes is so easy that new genes can affect human health. Helle Montinen sees the importance of working on a larger scale, for example in understanding the basic principles of biological life.

“The emergence of new genes from nothing has astounded researchers. We now have an elegant model for the evolution of RNA genes.”

Although the findings are based on small regulatory genes, the researchers believe the findings can be generalized to other genes and RNA molecules. For example, using the raw materials generated by the newly discovered mechanism, natural selection may create more complex RNA structures and functions.

The study was published in With people.

Reference: “De novo generation of miRNAs from template switching during DNA replication” by Heli AM Mönttinen, Mikko J. Frilander and Ari Löytynoja, 29 November 2023, Proceedings of the National Academy of Sciences.
doi: 10.1073/pnas.2310752120