In 2010, researchers searching viral DNA came across 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 discovered fragments of a human gene. Not just any gene either. It was a brain-associated virus and appeared to have copied itself into the virus’s genetic material.
For reasons that have little to do with the significance of the discovery, it remained unpublished for more than a decade. But when scientists finally returned to investigate, they discovered something even stranger.
The human gene, known as BC200, had been copying itself to new locations for tens of millions of years. And although it has acquired a specialized role in our cells, it has apparently never lost this ability.
The strange DNA that doesn’t stay put
It’s tempting to imagine DNA as a stable instruction manual, with genes located at fixed addresses along our chromosomes.
But DNA is much more agitated.
Nearly half of human DNA is made up of sequences derived from transposable elements, sometimes called skipping genes. These portions 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 position in corn chromosomes. His work ultimately earned him a Nobel Prize.
Most of the jumping elements in the human genome have long since lost their mobility.
Sometimes, however, evolution recruits one of these elements for an entirely new purpose. When this happens, the element usually becomes a permanent part of the cell’s genetic machinery, thereby abandoning its former ability to move.
BC200 seems to have done something different.
A brain gene with a secret identity
BC200 is an unusual gene because it does not produce protein.
Instead, it produces a small noncoding RNA molecule, about 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. However, its precise physiological role remains incompletely understood.
BC200 also has a much older evolutionary identity.
About 40 million years ago, in an ancestor of modern apes, a mobile genetic element was transformed into what eventually became the BC200 gene.
According to the conventional evolutionary picture, this should have marked the end of his jumping days.
But new research suggests otherwise.
By examining the genetic sequences of humans and other primates, the researchers found that BC200 continued to generate copies of itself long after it acquired cellular function.
“Genes that originate from transposable elements and are repurposed for cellular functions are generally no longer transposable,” Cedric Feschotte, a molecular biologist at Cornell University and lead author of the study, explained in a university release.
“Somehow evolution has failed to disentangle these two things,” he added.
How does human DNA turn into viruses?
Researchers suspect that BC200 borrowed machinery from another mobile genetic element called LINE-1.
LINE-1 elements are among the rare jumping elements still active in humans. Rather than cutting themselves from the DNA, they use a copy-and-paste mechanism. DNA is transcribed into RNA, which the LINE-1 machinery converts back to DNA and inserts elsewhere in the genome.
BC200 seems to exploit this machinery to copy itself. The researchers suspect that the same process occurred when the molluscum contagiosum virus infected human skin cells, allowing BC200 RNA to be copied into the viral genome.
The study did not 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 that viruses can sometimes carry genetic material between otherwise unrelated organisms.
Could this jumping gene affect human health?
The RNA is expressed at abnormal levels in some cancers and has also been found at elevated levels in the brains of people with Alzheimer’s disease.
This does not establish that BC200 causes any of these conditions, nor does it establish that its ability to jump contributes to the disease.
But mobile genetic elements can sometimes cause mutations when they insert into new genomic locations. The researchers now want to check whether BC200 generates new insertions in cancer cells and whether these changes have biological consequences.
Another mystery concerns the virus itself. Did the molluscum contagiosum virus simply acquire BC200 by accident, or does carrying the sequence provide an advantage when infecting human cells?
For the moment, no one knows.
The most important finding is that evolution did not necessarily force BC200 to choose between being a useful cellular gene and a mobile genetic element. For about 40 million years, it seems to be both.
The research results were published in Scientific reports.
Gn Health
