Scientists published findings on September 24 in Science showing that BC200, a human brain gene derived from an ancient jumping gene, still moves and copies itself through genomes after being identified inside a human poxvirus.
Researchers Trace Origins of the Mobile Brain Gene BC200
Long before it became associated with human neurons, the evolutionary ancestor of BC200 was a transposon. Transposons, commonly referred to as jumping genes, are stretches of DNA capable of changing their position within a genome. While they account for about half of the human genome, the vast majority of these elements became inactive over millions of years as they were repurposed for cellular functions. Most genetic sequences derived from transposons lost their mobility long ago.
First identified in the late 1980s as an abundant non-coding RNA in human neurons, the gene is found exclusively in humans and closely related primates. Although its precise physiological role is under investigation, evidence suggests it may be involved in regulating the translation of neuronal messenger RNAs into proteins. It also appears in low levels in germ cells, including sperm and eggs, opening the possibility that its movements could generate inheritable insertions. BC200 broke that rule.
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, Feschotte added
Nobel Prize winner Barbara McClintock, Class of 1923, M.A. 1925, Ph.D. 1927, discovered transposons in the 1940s. The researchers first identified BC200 in 2010 when Feschotte was a faculty member at the University of Texas at Arlington, and Cheng Sun was a postdoctoral researcher in a joint lab with Ellen Pritham, who was then an assistant professor at the University of Texas at Arlington. Co-authors of the work also include Cheng Sun, a professor of evolutionary genomics at Capital Normal University in Beijing, China. Financial support for the research was provided by the National Natural Science Foundation of China, the University of Texas at Arlington, and Cornell University.
Scientists Spot the Gene Inside the Molluscum Contagiosum Virus
The discovery came from examining viral genomes rather than human tissue. The team suspects the genetic transfer occurred while the virus was infecting human skin cells, which represent the only known cellular host for the pathogen.
Researchers note that a progenitor of BC200 was co-opted in a common primate ancestor from an ancient transposon roughly 40 million years ago, but it has managed to jump into the molluscum contagiosum virus twice within modern human history since the era of Homo sapiens
, approximately 100,000 years ago.
Investigators Connect BC200 to Cancer and Alzheimer’s Disease
Beyond its normal expression in healthy neurons, BC200 shows abnormal activity in diseased tissue. Scientists have detected the gene aberrantly expressed in some tumors, including breast cancer, and present in elevated amounts in the brains of people with Alzheimer’s disease. These observations create questions about whether the gene’s active jumping capability contributes directly to cellular mutations or disease progression.
Researchers currently have no evidence that BC200 directly causes cancer or Alzheimer’s disease. However, the discovery of its mobility gives scientists a new framework to investigate. The team aims to determine whether the molluscum contagiosum virus exploits BC200 to manipulate human host cells, and whether the gene is actively jumping inside cancer cells to create harmful genomic instability.