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New study reveals hidden regulatory roles of “junk” DNA

2025-07-18
(Press-News.org) A new international study suggests that ancient viral DNA embedded in our genome, which were long dismissed as genetic “junk”, may actually play powerful roles in regulating gene expression. Focusing on a family of sequences called MER11, researchers from Japan, China, Canada, and the US have shown that these elements have evolved to influence how genes turn on and off, particularly in early human development.

 

Transposable elements (TEs) are repetitive DNA sequences in the genome that originated from ancient viruses. Over millions of years, they spread throughout the genome via copy-and-paste mechanisms. Today, TEs make up nearly half of the human genome. While they were once thought to serve no useful function, recent research has found that some of them act like “genetic switches”, controlling the activity of nearby genes in specific cell types.

 

However, because TEs are highly repetitive and often nearly identical in sequence, they can be difficult to study. In particular, younger TE families like MER11 have been poorly categorized in existing genomic databases, limiting our ability to understand their role.

 

To overcome this, the researchers developed a new method for classifying TEs. Instead of using standard annotation tools, they grouped MER11 sequences based on their evolutionary relationships and how well they were conserved in the primate genomes. This new approach allowed them to divide MER11A/B/C into four distinct subfamilies, namely, MER11_G1 through G4, ranging from oldest to youngest.

 

This new classification revealed previously hidden patterns of gene regulatory potential. The researchers compared the new MER11 subfamilies to various epigenetic markers, which are chemical tags on DNA and associated proteins that influence gene activity. This showed that this new classification aligned more closely with actual regulatory function compared with previous methods.

 

To directly test whether MER11 sequences can control gene expression, the team used a technique called lentiMPRA (lentiviral massively parallel reporter assay). This method allows thousands of DNA sequences to be tested at once by inserting them into cells and measuring how much each one boosts gene activity. The researchers applied this method to nearly 7000 MER11 sequences from humans and other primates, and measured their effects in human stem cells and early-stage neural cells.

 

The results showed that MER11_G4 (the youngest subfamily) exhibited a strong ability to activate gene expression. It also had a distinct set of regulatory “motifs,” which are short stretches of DNA that serve as docking sites for transcription factors, the proteins that control when genes are turned on. These motifs can dramatically influence how genes respond to developmental signals or environmental cues.

 

Further analysis revealed that the MER11_G4 sequences in humans, chimpanzees, and macaques had each accumulated slightly different changes over time. In humans and chimpanzees, some sequences gained mutations that could increase their regulatory potential during in human stem cells.Young MER11_G4 binds to a distinct set of transcription factors, indicating that this group gained different regulatory functions through sequence changes and contributes to speciation,leading researcher Dr. Xun Chen explains.

 

The study offers a model for understanding how “junk” DNA can evolve into regulatory elements with important biological roles. By tracing the evolution of these sequences and directly testing their function, the researchers have demonstrated how ancient viral DNA has been co-opted into shaping gene activity in primates.

 

“Our genome was sequenced long ago, but the function of many of its parts remain unknown", co-responding auther Dr. Inoue notes. Transposable elements are thought to play important roles in genome evolution, and their significance is expected to become clearer as research continues to advance.

END


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[Press-News.org] New study reveals hidden regulatory roles of “junk” DNA