In 2010, researchers searching through viral DNA stumbled upon something that didn’t belong there.
Inside the genome of a virus (molluscum contagiosum virus) that causes small, wart-like bumps on human skin, they found pieces of a human gene. Not just any gene, either. It was one associated with the brain, and it appeared to have copied itself into the virus’s genetic material.
For reasons that had little to do with the discovery’s importance, the finding remained unpublished for more than a decade. But when scientists finally returned to investigate, they uncovered something even stranger.
The human gene, known as BC200, had been copying itself into new locations for tens of millions of years. And despite acquiring a specialized role in our cells, it had apparently never lost that ability.
The strange DNA that won’t stay put
It’s tempting to imagine DNA as a stable instruction manual, with genes sitting at fixed addresses along our chromosomes.
But DNA is way more restless.
Nearly half of human DNA consists of sequences derived from transposable elements, sometimes called jumping genes. These stretches of genetic material can copy themselves or move to new locations within a genome.
Their discovery dates back to the 1940s, when geneticist Barbara McClintock showed that certain genetic elements could change positions in maize chromosomes. Her work eventually earned her a Nobel Prize.
Most jumping elements in the human genome have long since lost their mobility.
Occasionally, however, evolution recruits one of these elements for an entirely new purpose. When that happens, the element usually becomes a permanent part of the cell’s genetic machinery, surrendering its old ability to move.
BC200 appears to have done something different.
A brain gene with a secret identity
BC200 is an unusual gene because it doesn’t produce a protein.
Instead, it produces a small molecule of noncoding RNA, approximately 200 building blocks long, that is particularly abundant in neurons.
Scientists believe this RNA helps regulate how messenger RNA molecules are translated into proteins, potentially influencing when and where neurons produce the proteins they need. Its precise physiological role, however, remains incompletely understood.
BC200 also has a much older evolutionary identity.
Roughly 40 million years ago, in an ancestor of modern monkeys and apes, a mobile genetic element was repurposed into what eventually became the BC200 gene.
Under the conventional evolutionary picture, that should have marked the end of its jumping days.
But the new research suggests otherwise.
By examining genetic sequences from humans and other primates, the researchers found that BC200 had continued generating copies of itself long after acquiring its cellular function.
“Genes that come from transposable elements and that are repurposed for cellular functions are typically no longer transposable,” Cedric Feschotte, a molecular biologist at Cornell University and senior author of the study, explained in a university statement.
“Somehow evolution hasn’t been able to untangle these two things,” he added.
How does human DNA jump into a virus?
The researchers suspect BC200 borrowed machinery from another mobile genetic element called LINE-1.
LINE-1 elements are among the few jumping elements still active in humans. Rather than cutting themselves out of DNA, they use a copy-and-paste mechanism. DNA is transcribed into RNA, which LINE-1 machinery converts back into DNA and inserts elsewhere in the genome.
BC200 appears to exploit this machinery to make copies of itself. Researchers suspect the same process occurred when molluscum contagiosum virus infected human skin cells, allowing BC200 RNA to be copied into the viral genome.
The study didn’t directly observe this transfer, but genetic evidence points to LINE-1 as the likely mechanism.
Similar transfers have occurred elsewhere in nature. Scientists previously identified a snake-derived transposon in a rodent poxvirus, suggesting viruses can sometimes shuttle genetic material between otherwise unrelated organisms.
Could this jumping gene affect human health?
The RNA is expressed at abnormal levels in certain cancers and has also been found at elevated levels in the brains of people with Alzheimer’s disease.
That doesn’t establish that BC200 causes either condition, or that its ability to jump contributes to disease.
But mobile genetic elements can sometimes cause mutations when they insert into new genomic locations. The researchers now want to investigate whether BC200 generates new insertions in cancer cells and whether those changes have biological consequences.
Another mystery concerns the virus itself. Did molluscum contagiosum virus simply acquire BC200 by accident, or does carrying the sequence provide some advantage when infecting human cells?
For now, nobody knows.
The larger discovery is that evolution hasn’t necessarily forced BC200 to choose between being a useful cellular gene and a mobile genetic element. For roughly 40 million years, it appears to have been both.
The research findings were published in Science Reports.
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