ITHACA, N.Y. – Until now, no one has observed a human gene that is both mobile and required for bodily functions.
Scientists at Cornell University found a human genetic element in a poxvirus and discovered it was both an important gene for brain function and a jumping gene capable of moving and inserting itself in genomes.
A study published Sept. 24 in Science reports that the gene, called BC200, combines a mix of characteristics that have never been seen before.
BC200 is mostly expressed in neurons but originated millions of years ago from a transposon or ‘jumping gene’, a non-coding genetic element known for its ability to move and insert itself in genomes.
Transposons can insert blocks of DNA in a gene and disrupt function, leading to disease, but in the long-term they can be a constructive force in evolution to regulate or assemble new beneficial genes. While transposons account for half of human DNA, most of them are inactive, with a very small number of them remaining mobile and able to replicate within genomes.
“Genes that come from transposable elements and that are repurposed for cellular functions are typically no longer transposable,” said Cedric Feschotte , a senior author of the study. “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.”
There have been a few other documented cases of transposable elements in other species inserting in viruses, including in the late 1980s when researchers in a lab setting documented for the first time the insertion of a transposon from moth cells they were studying in culture to a baculovirus, known to infect insects.
BC200 is only found in humans and related primates and was discovered in the late 1980s as an abundant non-coding RNA in human neurons. Although BC200’s physiological function is poorly understood, evidence suggests it may be involved in regulating the translation of neuronal messenger RNAs into proteins. It is also found in low levels in germ cells – sperm and eggs – making it potentially capable of generating inheritable insertions in other areas of the genome.
The researchers also suspect that it jumped in skin cells since these are the only cells known to be infected by molluscum contagiosum virus (MCV). The gene is also aberrantly expressed in some tumors and overexpressed in the brains of Alzheimer’s disease patients, suggesting its jumping ability could also play roles in these diseases.
Feschotte said he and colleagues would like to explore whether the molluscum contagiosum virus is using BC200 for its own purpose of manipulating human host cells. They are also interested in better understanding the gene’s role in disease, such as breast and other types of tumors, where it is abnormally expressed, and whether it is jumping in cancer cells and causing mutations.
For additional information, read this Cornell Chronicle story.
Cornell University has dedicated television and audio studios available for media interviews.
-30-
Science