Some parts of our DNA can copy themselves to new locations. Copies derived from a gene active in human brain cells appear to have taken that journey further: into a virus. The researchers found two such sequences, derived from a gene called BC200, within the molluscum contagiosum virus, which infects our skin and causes small, raised lesions. The discovery reveals an unusual genetic double life. BC200 acquired a cellular function millions of years ago, but retained the ability to make copies that insert into other places. A study published in Science suggests that this movement has continued throughout primate evolution, contributed to differences between human genomes, and transported sequences derived from BC200 across the boundary between humans and a virus. But the virus did not simply take a gene from a brain cell, and there is nothing to suggest that it has acquired anything resembling brain function. What these sequences actually do within the virus is still unknown. BC200 works differently than most genes: It completely skips the step of encoding a protein and instead produces a short RNA molecule, one that is especially abundant in neurons. Laboratory experiments suggest that this RNA helps regulate protein production. However, its precise physiological function remains poorly understood. Just because a gene is especially active in a tissue does not mean that its DNA exists only there. Most cells with a nucleus carry essentially the same genetic information. What differs is which genes they use and in what quantity. Calling BC200 a “brain gene” describes its activity in neurons. Its origins lie in a transposable element, one of the mobile DNA sequences often called “jumping genes.” Some make copies of themselves that enter new locations while the original remains in place. A predecessor of BC200 was established in a common ancestor of monkeys and apes approximately 35 to 55 million years ago. About 40 million years ago, it was recruited to perform a cellular function, apparently in regulating protein production in neurons. This recruitment is usually accompanied by a loss of mobility. BC200 appears to have retained both capabilities. “Somehow evolution has not been able to disentangle these two things,” Cedric Feschotte of the Department of Molecular Biology and Genetics at Cornell University says in a university statement. (Kateryna Kon/Science Photo Library/Getty Images) elements.Two sequences derived from BC200 stood out in molluscum contagiosum virus. One covered the entire Alu-derived domain of the human gene, a region inherited from its mobile ancestor. The other was shorter and incomplete at both ends. So what appeared in the virus are fragments derived from BC200, not a complete, intact copy of the gene itself. Several clues pointed to a human origin. BC200 occurs in humans and related primates, while molluscum contagiosum virus is only known to infect humans in the wild. The researchers found no corresponding elements in other poxvirus genomes they examined, including a closely related virus that infects horses. The analysis pointed to two separate transfer events, not a single insertion that was later duplicated within the virus. The likely mechanism involves LINE-1, another mobile genetic element capable of producing the molecular machinery to copy RNA into DNA and insert it into a genome. BC200 has no transport machinery of its own, so it travels on LINE-1, borrowing equipment from another element to make the jump. Genetic signatures surrounding viral insertion supported this explanation. However, the team reconstructed the transfer from DNA evidence, rather than observing how it happened. Although BC200 RNA is abundant in neurons, it is also expressed at low levels in the skin. The researchers found increased expression of BC200 in cultured human fibroblasts infected with the virus. That suggests the infection could help create conditions for transfer, without directly establishing where the historical events occurred. The team then examined sequencing data from 908 people, identifying eight insertions derived from BC200 that varied between individuals. Two were widespread across five continental population groups, suggesting ancient origins. Another was largely restricted to African individuals. The remaining five were rarer: one occurred in only two people, while four were each detected in a single individual. These rare insertions suggest very recent activity. However, being detected in a person does not establish that an insertion has arisen during that person’s lifetime. Among anthropoid primates, the researchers also identified hundreds of lineage-specific insertions, placing the viral discovery within millions of years of continuous movement. It remains uncertain whether the virus benefits. The team found evidence that its BC200-derived sequences are transcribed into RNA. Such RNA could help manipulate protein production in infected cells, but that possibility still needs to be tested. The study does not prove that the virus has become more dangerous. Instead, it shows that acquiring a cellular function does not have to put an end to the mobility of a genetic element. BC200’s combination of function and movement makes the boundary between genes and jumping DNA appear more flexible than expected. The research has been published in Science. This article was fact-checked by Fiona MacDonald and edited by Fiona MacDonald. While we take pride in our process, we are human. If you spot an error, please let us know.
