Human Brain Gene Has Been Caught Jumping Into a Virus That Causes Skin Growths

Scientists have found a human gene that does two things biology textbooks say should not go together: it performs a real job in the brain, and it can still copy itself and jump around the genome. The evidence came from an unlikely place, the DNA of a common poxvirus that causes small skin growths.

The gene, called BC200, makes a noncoding RNA that is abundant in human neurons and is thought to help regulate how neuronal messenger RNAs are turned into proteins. It descends from a transposon, or "jumping gene," a stretch of DNA that can insert copies of itself elsewhere in a genome. Transposons make up roughly half of human DNA, but almost all of them are dead, their ability to move long since broken by mutations. When evolution repurposes a transposon for a useful job, it usually stops jumping.

BC200 did not. In a study published in Science, a team led by first author Pu Gao and Cheng Sun of Capital Normal University in Beijing, with Cedric Feschotte of Cornell University and Ellen Pritham, found two insertions of BC200 inside the genome of molluscum contagiosum virus, a widespread and mostly harmless human poxvirus that produces wart-like bumps. "Genes that come from transposable elements and that are repurposed for cellular functions are typically no longer transposable," Feschotte said. "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."

The researchers traced BC200's ancestor back roughly 40 million years to an ancient transposon taken up by a common primate ancestor. The gene is found only in humans and closely related primates. Its two jumps into the virus happened within the era of modern humans, about 100,000 years ago. Because molluscum contagiosum infects only skin cells, the team believes BC200 made those leaps in human skin.

Sun first spotted the viral insertions in 2010 while he was a postdoctoral researcher in Feschotte and Pritham's lab at the University of Texas at Arlington, but the group never published. Years later, Sun told Feschotte at a conference that he and Gao had revived the project. "I can't believe we never got scooped on this," Feschotte said.

Only a handful of transposons have ever been caught escaping into viruses. In the late 1980s, researchers saw a moth transposon hop into a baculovirus in lab cultures, and in 2007 a Japanese team found a snake-derived element in a rodent poxvirus. The finding raises the possibility that viruses can ferry genetic elements between hosts.

The work also has medical implications. BC200 is present at low levels in sperm and egg cells, meaning its jumps could be inherited. It is abnormally active in some tumors, including breast cancer, and overexpressed in the brains of people with Alzheimer's disease. The team now wants to learn whether the virus uses BC200 to manipulate infected cells, and whether the gene jumps in cancer cells and causes mutations there.