A Gene From the Human Brain Leapt Into a Virus—and Scientists Have No Idea What It’s Doing There

Here’s what you'll learn when you read this story:

• Researchers have identified a gene that combines characteristics never before seen together in a single gene.

• This “jumping gene,” which also plays a role in brain function, can copy and insert itself elsewhere in the genome—and it has turned up in troubling places, including diseased cells.

• It’s the first human gene known to be mobile that also appears to serve a normal cellular function—and it’s even escaped into a poxvirus.

The gene BC200 has been known for decades, but a new look at its behavior raises quite a few questions—and the answers aren’t all encouraging. In a first, researchers found that this “jumping gene” appears to serve an important role in human neurons even as it continues to copy itself into new locations, including, at some point during modern human history, the genome of a human poxvirus.

Writing in the September 24 issue of Science, a team from Cornell University, Capital Normal University in Beijing, and the University of Texas at Arlington concluded that BC200’s mix of traits has never been documented in a gene before. The gene, they concluded, “blurs the line between gene and transposon, combining stable function with persistent mobilization, including a recent escape into a human poxvirus.”

A transposon—better known as a jumping gene—has an unusual ability: it can copy itself into a new spot in the genome, and if it lands inside an existing gene, it can disrupt that gene’s normal function, sometimes causing disease. But transposons can also use their powers for good; over millions of years, the researchers wrote, they can be domesticated into useful regulators of other genes. In fact, the team noted, transposons account for roughly half of all human DNA, though the vast majority have long since gone inert, and only a minuscule fraction remain mobile. What scientists had never seen until now was a human gene that is simultaneously mobile and necessary for a cellular function. BC200 changes that.

“Genes that come from transposable elements and that are repurposed for cellular functions are typically no longer transposable,” Cédric Feschotte, a professor in Cornell’s Department of Molecular Biology and Genetics and senior author of the study, said in a statement. “BC200 was itself created from a mobile element but has retained its mobility, and yet it is also clearly serving a cellular function. Somehow evolution hasn’t been able to untangle these two things.”

Exactly what that cellular function is, however, remains unsettled. BC200 was first described in the late 1980s as a non-coding RNA in human neurons, and the leading theory holds that it helps regulate the translation of neuronal messenger RNAs into proteins. The gene is also expressed at low levels in germ cells—think sperm and eggs—which means that any new copies it makes there could be passed down to future generations.

Taken together, the findings suggest that at some point over millions of years, BC200 acquired a cellular role without ever losing its ability to copy and paste itself back into the genome.

That lingering mobility is the troublesome part. Searching genomic databases, the team found two copies of BC200 lodged in the genome of molluscum contagiosum virus (MCV), the largely benign poxvirus behind the wart-like skin bumps of the same name. Because skin cells are the only cells MCV is known to infect, the researchers suspect that’s where the transfers happened. The gene also shows up abnormally in some tumors, including breast cancers, and at elevated levels in the brains of people with Alzheimer’s disease, “suggesting its jumping ability could also play roles in these diseases,” according to the statement.

The research team now hopes to better understand BC200 and its possible contributions to illness—in particular, whether the gene is jumping into the genomes of cancer cells and creating mutations there.