Researchers at Lund University have identified a viral remnant carried in the chimpanzee genome that shuts down a gene active in humans and involved in early brain development. The study, published in Science Advances, used human and chimpanzee stem cells to grow miniature brain models and found the gene, LINC00662, switched on in the human tissue and silent in the chimpanzee tissue. According to Mirage News, the work points to a single viral insertion as the cause.
The virus in question belongs to a group called endogenous retroviruses. This one, known as PTERV1, infected chimpanzees millions of years ago, and its genetic material stayed in the animals' DNA, passing down through later generations. The researchers found that PTERV1 had copied itself into many places in the chimpanzee genome, and that those viral sequences are consistently shut off through methylation, a process that governs whether genes are active or inactive.
Why it matters
Humans and chimpanzees share most of their genetic material, so the two species are close relatives at the level of DNA. The new findings suggest that some of the difference between them lies not in which genes they carry but in which genes are switched on. Johan Jakobsson, Professor of Molecular Neurogenetics at Lund University, said the results show that a virus can alter a DNA sequence across an entire population. He noted that the virus his team studied affected chimpanzees specifically, which makes the comparison with humans useful for understanding how gene regulation differs between the two.
Jakobsson said the findings indicate that LINC00662 plays a meaningful part in early human brain development, and that the work helps explain how gene regulation can either protect the brain or cause it harm.
Miniature brains grown from stem cells
To see how the viral remnant affected brain development, the team used stem cells from both species to produce brain organoids. These are three-dimensional clusters of tissue that resemble real brain material and can reproduce some features of early brain development. When the researchers compared the organoids, they found LINC00662 active in the human versions and completely switched off in the chimpanzee versions.
Patricia Gerdes, a postdoc in molecular neurogenetics at Lund University, said the gene was strongly expressed in the human organoids and not at all in the chimpanzee ones.
The team then tested whether the viral sequence was actually responsible. Using the CRISPR-Cas9 gene-editing tool, they cut the viral DNA out of chimpanzee cells. With the viral remnant gone, the gene was expressed again. Gerdes said this demonstrates that the viral insertion is what causes the gene to be switched off in chimpanzees.
What the gene appears to do
The researchers also looked at what LINC00662 does in humans. When they used CRISPR to silence it in human brain organoids, the activity of genes involved in the development of nerve cells dropped, as did the activity of genes involved in forming connections between those cells.
That result supports the broader idea that humans and their closest living relatives differ not only in the genes they possess but also in which of those genes are turned on. The study's authors plan to examine whether other viral remnants had comparable effects during the evolution of the brain, and whether this kind of DNA sequence is connected to brain diseases.
Watch for follow-up work from the Lund group on other retroviral remnants and any possible link between LINC00662 and neurological disease.
