“Junk” DNA Reveals Hidden Power: Ancient Viruses Found to Regulate Human Gene Expression
A groundbreaking international study reveals that so-called “junk” DNA – remnants of ancient viral infections embedded in our genome – plays a surprisingly powerful role in regulating gene activity, particularly during early human development. The research, conducted by teams from Japan, China, Canada, and the US, challenges long-held assumptions about the function of non-coding DNA and opens new avenues for understanding human evolution and disease.
The Genome’s Hidden Regulators
For decades, scientists believed that transposable elements (TEs) – repetitive DNA sequences originating from ancient viruses – were largely inactive vestiges of past infections. These elements comprise nearly half of the human genome, spreading through a “copy-and-paste” mechanism over millions of years. However, recent investigations have hinted at a more complex role, suggesting some TEs act as “genetic switches,” controlling the activity of nearby genes in specific cell types.
The challenge lay in studying these elements. Due to their repetitive nature and sequence similarity, TEs are notoriously difficult to categorize and analyze. This was particularly true for younger families of TEs, like MER11, which were poorly represented in existing genomic databases.
A New Classification System Unlocks Secrets
To overcome these hurdles, researchers developed a novel method for classifying TEs. Instead of relying on standard annotation tools, they grouped MER11 sequences based on their evolutionary relationships and degree of conservation across primate genomes. This innovative approach allowed them to divide MER11A/B/C into four distinct subfamilies – MER11_G1 through G4 – representing an evolutionary timeline from oldest to youngest.
This refined classification immediately revealed previously hidden patterns of gene regulatory potential. By comparing the new MER11 subfamilies to epigenetic markers – chemical tags on DNA and associated proteins that influence gene activity – the team found a stronger correlation between the new classification and actual regulatory function than with previous methods.
Direct Evidence of Regulatory Control
To directly test whether MER11 sequences could control gene expression, the researchers employed a technique called lentiMPRA (lentiviral massively parallel reporter assay). This method allows for the simultaneous testing of thousands of DNA sequences by inserting them into cells and measuring their impact on gene activity. Applying this technique to nearly 7,000 MER11 sequences from humans and other primates, they analyzed their effects in human stem cells and early-stage neural cells.
The results were striking. MER11_G4, the youngest subfamily, demonstrated a particularly strong ability to activate gene expression. It also possessed a unique set of regulatory motifs – short DNA stretches that serve as docking sites for transcription factors, the proteins responsible for turning genes on and off. These motifs can significantly influence how genes respond to developmental signals and environmental cues.
Evolution and Speciation
Further analysis revealed that MER11_G4 sequences in humans, chimpanzees, and macaques had accumulated distinct changes over time. Notably, in both humans and chimpanzees, certain sequences gained mutations that appeared to enhance their regulatory potential 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,” explained a leading researcher, Dr. Xun Chen.
The study provides a compelling model for understanding how “junk” DNA can evolve into crucial regulatory elements. By tracing the evolutionary history of these sequences and directly testing their function, the researchers have demonstrated how ancient viral DNA has been co-opted to shape gene activity in primates.
“Our genome was sequenced long ago, but the function of many of its parts remain unknown,” noted a corresponding author, Dr. Inoue. “Transposable elements are thought to play important roles in genome evolution, and their significance is expected to become clearer as research continues to advance.”
Source: Journal reference: Chen, X., et al. (2025) A phylogenetic approach uncovers cryptic endogenous retrovirus subfamilies in the primate lineage. Science Advances. doi.org/10.1126/sciadv.ads9164.
