Researchers at Cornell University have identified a human gene that appears to serve an important biological role while still retaining the ability to move around the genome — a combination not previously seen in a human gene.
The gene, BC200, is expressed mainly in neurons. Its evolutionary history traces back millions of years to a transposon, also known as a jumping gene: a non-coding genetic element capable of relocating itself and inserting into new places in a genome.
The discovery arrived from an unexpected direction. The team found a human genetic element inside a poxvirus, and analysis showed the element was BC200.
About half of the human genome is made up of transposon-derived DNA. Most of those elements are no longer active, and only a very small fraction can still move and copy themselves within genomes.
Genes built from such elements normally lose their mobility in the course of being put to work. "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."
BC200 is found only in humans and closely related primates, and was first identified in the late 1980s as a highly abundant non-coding RNA in human neurons. Its exact physiological role remains uncertain, though evidence suggests it may help regulate how neuronal messenger RNAs are translated into proteins.
The researchers think BC200 made its jump into the molluscum contagiosum virus while the virus was infecting skin cells, since those are the only cells the virus is known to infect.
Transposable elements have been observed moving into viruses before, though rarely. One early example came in the late 1980s, when researchers working with cultured moth cells saw a transposon move from those cells into a baculovirus, a type of virus that infects insects. BC200 also appears at low levels in germ cells, which means it may have the potential to create new insertions in the genome that could be inherited by future generations.
The finding leaves an administrative question that the biology does not settle. BC200 is a human gene. BC200 is also in a virus. Both statements come from the same paper, and only one of them fits on a form.
Our analysts note that the usual tests are no help here. Residence fails, because the gene is resident in both. Origin fails, because it originated in neither: it came from a transposon, which had already moved once. Function fails, because the gene is functioning in human neurons while simultaneously being somewhere else entirely, which is the point of the paper.
The strongest position available is the gene’s own. It was built out of a mobile element, kept the mobility, and has now exercised it. Evolution, in Feschotte’s words, hasn’t been able to untangle these two things, and neither can anybody else, because untangling is precisely what the gene declines to do.
The Department of Unnecessary Research has accordingly stopped asking whose gene it is. Half the human genome is made of elements that arrived from somewhere else, and almost all of them have settled down. One has not. It is a human gene with a forwarding address.