UC Irvine Researchers Explore Role of Viral-Derived DNA in Disease Response

What role does viral-derived DNA play in controlling cellular activity and generating new genes that are important for cell differentiation and our response to diseases?

Researchers at UC Irvine are one step closer to answering this question after identifying hundreds of new genes that contain viral-derived elements present in our genome.

“Ninety percent of disease mutation occurs in the area of the genome that is non-coding,” says Ivan Marazzi, PhD, director of the Center for Epigenetics & Metabolism and a professor of biological chemistry at UC Irvine. A major component of this “non-coding area” is transposable elements (TEs), which contain the remnants of ancient viruses embedded into our genetic code.

A new experimental study conducted by an international team investigated when, where and how TEs become part of a gene. The team — led by the Marazzi Lab and by the UCI Systems Genetics Lab, directed by Marcus Seldin, PhD — included UC Irvine postdoc researcher Youngseo Cheon and PhD student Erik Alvstad.

Their findings, published in an article in Nature Structural & Molecular Biology, unveil mechanisms by which viral-derived elements enhance transcriptome plasticity — that is, a gene’s ability to alter its response to environmental stress.

“Fifty percent of our genome is viral-derived,” says Marazzi, explaining that most of these TE sequences are scattered around the genome and are repetitive, so they’re usually discarded. “Using long-read genome sequencing, we mapped the compendium of these genes in all cell types of humans and mice and described how they work in making novel gene isoforms.” For example, the article describes a long viral-derived RNA that can make stem cells become totipotent (capable of developing into a complete organism), which Marazzi calls “a striking result that could help regenerative medicine.”

The researchers are thus excited to establish a framework for characterizing TEs. “We now can look at most of our genome and transcriptome, whereas before we were only looking at 50 percent,” says Seldin, adding that this will let them determine whether a mutation in a viral-derived element causes disease in humans. “Every human has different viral-derived elements, or structural variants, so our work allows us to identify new mutations linked to diseases.”