DNA that humans acquired from ancient viruses plays a key role in switching parts of our genetic code on and off, a new study has found.
Nearly half of the human genome consists of segments called transposable elements (TEs), also known as “jumping genes” because they can hop around the genome. Some of these TEs are remnants of ancient viruses that embedded themselves in our ancestors’ genomes and have been passed down over millions of years.
For decades after TEs were discovered, scientists assumed they served no useful purpose — that they were “junk” DNA. But this new study adds to the mounting evidence that this description was far from correct.
Far from being functionless fossils, these ostensibly dormant stretches of our DNA could be crucial in regulating gene expression, especially during early development, the research suggests. The scientists published their findings July 18 in the journal Science Advances.
“Our genome was sequenced long ago, but the function of many of its parts remain unknown,” study co-author Hiromi Nakao-Inoue, a research coordinator at Kyoto University’s Institute for the Advanced Study of Human Biology, said in a statement. “Transposable elements are thought to play important roles in genome evolution, and their significance is expected to become clearer as research continues to advance.”
Not so junky after all
TEs were deemed “junk” because they seemed irrelevant to the creation of proteins — the molecules that build cells and keep them running. While genes carry blueprints for proteins, these repetitive, transposable elements had long been dismissed as “nonfunctional” DNA.
Related: Best-ever map of the human genome sheds light on ‘jumping genes,’ ‘junk DNA’ and more
Yet in recent years, evidence has begun to pile up that these repetitive portions of our genomes play a role in gene regulation. For instance, their codes are often used to make noncoding RNA, a molecule that can act upon other genes to differentiate cells and regulate the growth of embryos.
More detailed study of transposable elements has also been made possible by CRISPR. The famous gene-editing tool has enabled scientists to peer into how TEs influence the structure of chromatin — the mixture of DNA and proteins from which chromosomes are made — and jump-start an embryo’s gene activity after fertilization.
The scientists behind the new research focused on a specific family of TEs called MER11. The family belongs to a larger class of TEs that entered primate genomes some 40 million years ago.
The researchers classified sequences within the MER11 family based on their evolutionary relationships to one another. This produced four subgroups from MER11_G1 (the oldest) to MER11_G4 (the youngest).
To see what effects these TEs have on cells, they inserted nearly 7,000 of the sequences into cells in lab dishes. The sequences, taken from humans and other primates, were placed inside stem cells and early-stage neural cells, whose gene activity was then measured.
Their results showed that the youngest members of the MER11 family — MER11_G4 — had a strong ability to activate genes. They came equipped with unique “transcription factor binding sites,” which are DNA motifs that are key to development and act as docking pads for proteins that control gene expression.
Subtle variations in MER11_G4 sequences also existed between humans, chimps and macaques, with variations changing the sequences’ regulatory effect from species to species.
“The study highlights how much there is still to learn from the genome sequence,” Cristina Tufarelli, a geneticist at the University of Leicester’s University’s Cancer Research Centre who was not involved in the study, told Live Science. “Especially when it comes to virus-like transposon repeats whose variety between and within families has been largely overlooked.”
She added that the work opens up several avenues for future investigation. “The approach could be applied to any transposable element with the potential to help gain a deeper knowledge of other elements with potential regulatory functions,” she said.
Tufarelli added that future experiments could involve deleting certain parts of the TEs with CRISPR to help unravel their roles in regulating gene expression in both health and disease.
