Scientists have discovered how our DNA can use a genetic fast-forward button to create new genes to quickly adapt to an ever-changing environment. While investigating DNA replication errors, researchers at Finland’s University of Helsinki discovered that certain single mutations create palindromes that are read the same way forward and backward. Under appropriate conditions, they can turn into microRNA (miRNA) genes.

These small, simple genes play an important role in regulating other genes. Many miRNA genes have existed for a long time in evolutionary history, but scientists have discovered that completely new miRNA genes have suddenly appeared in some groups of animals, such as primates.

“The sudden appearance of new genes fascinated researchers,” says bioinformatician Heli Monttinen, first author of the new study. “We now have an elegant model of RNA gene evolution.”

The errors that enable this high-throughput gene generation method are called template mutations (TSMs). The process of creation of TSM-associated microRNAs is much faster than the evolution of new functional proteins.

“DNA is copied one base at a time, and mutations are often single base errors, like wrong keystrokes on a laptop keyboard,” says project leader and bioinformatician Ari Loytinoia.

“We investigated the mechanism of creating larger errors, such as copying text from another context. We were particularly interested in cases where text was copied backwards to create a palindrome.”

All RNA molecules require repeated sequences of bases that lock the molecule into how it works. The team decided to focus on miRNA genes, which are extremely short, consisting of approximately 22 base pairs. However, even for simple miRNA genes, the chance of random base mutations gradually forming such palindromic cycles is very low.

Scientists are puzzled as to where these palindromic sequences come from. It appears that TSMs can rapidly generate complete DNA palindromes by creating new miRNA genes from previously non-coding DNA sequences.

“In an RNA molecule, bases of adjacent palindromes can combine to form hairpin-like structures. “Such structures are crucial for the functioning of RNA molecules,” says biotechnologist Mikko Freelander.

The complete genomes of many primates and mammals have already been mapped. By comparing these genomes with the help of a special computer algorithm, the researchers were able to find out which species had the palindromic microRNA pair.

“Thanks to detailed modeling of history, we were able to see that all palindromes were created by single mutational events,” explains Monttinen.

The diagram below illustrates the process well. Because DNA replication starts by going through every base pair in the recipe list, it stops when it hits a mutation or faulty base pair. The pattern then switches to the adjacent template and begins copying those instructions, but in the opposite direction. When the pattern returns to the original template, it combines with itself to form a small palindrome that can grow into a sharp structure.

Template switching during DNA replication allows a single mutation to create the perfect structure in DNA for a new miRNA gene. This is much more effective than the slow, incremental changes that can occur in individual building blocks. More than 6,000 such structures have been found in the primate family tree, which could lead to at least 18 completely new miRNA genes in humans. This accounts for 26 percent of all microRNAs thought to have evolved since the first appearance of primates.

Findings like these spanning evolutionary lines point to a universal mechanism for miRNA gene formation, and the team believes the findings could also be applied to other genes and RNA molecules. New miRNA genes that could potentially impact human health appear to emerge relatively easily. Some TSM-associated miRNAs, such as hsa-mir-576, affecting the antiviral response in primates, have already shown functional significance.

“Many TSM variants that can become miRNA genes are shared among human populations,” the authors write, “suggesting that the TSM process is active and currently shaping our genomes.”