A new international study suggests that what was once dismissed as “junk DNA” may actually play a crucial role in regulating gene expression.
The study focused on a group of transposable elements (TEs) embedded in the human genome.
TEs are repetitive DNA sequences that originated from ancient viruses. These genes can “jump” around and change their position on a chromosome.
After their discovery in 1983 by Barbara McClintock, TEs were thought to have no known biological function, earning them the nickname junk DNA.
However, recent studies have shown that this “junk”, which makes up nearly half of the human genome, may have a more important role to play.
“Our genome was sequenced long ago, but the function of many of its parts remain unknown,” says Dr Fumitaka Inoue, an author of the study from Kyoto University, Japan.
The team of researchers from Japan, China, Canada and the US focused their study on a relatively young family of TE sequences called MER11.
Considering this sequence has previously been poorly classified by existing genomic databases, the research team designed a new approach.
Instead of using standard annotation tools, they grouped the sequence into subfamilies ranging from oldest to youngest.
The team found this new classification method aligned more closely with actual regulatory function than previous models.
To test gene expression, the researchers used a technique called lentiviral massively parallel reporter assay (lentiMPRA), which allows thousands of DNA sequences to be tested at once.
They did this to measure the effects of almost 7,000 MER11 sequences on human and primate early-stage neural cells and stem cells.
The results showed the youngest subfamily, named MER11_G4, had a strong ability to activate gene expression and influenced how genes respond to external and developmental signals.
Comparing how some sequences mutated in different species – human, chimpanzee and macaque – revealed the MER11_G4 sequence had slightly changed over time.
“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,” says lead researcher Dr Xun Chen from the Shanghai Institute of Immunity and Infection.
This study demonstrates how ancient viral DNA has shaped gene activity in primates and further contributes to a growing field of literature trying to piece together the evolution of life.
“Transposable elements are thought to play important roles in genome evolution, and their significance is expected to become clearer as research continues to advance,” says Inoue.
The team’s results and new model for understanding TEs have been published in Science Advances.