Ancient virus suppresses brain gene in chimpanzees, study finds

Humans and chimpanzees share nearly identical genetic blueprints, yet their brains develop in drastically distinct ways. The answer, according to a study published in Science Advances, lies in an ancient retrovirus that infected chimpanzees millions of years ago.

Researchers at Lund University investigated how this historical infection left behind a genetic insertion known as PTERV1. Integrated into the chimpanzee genome long ago and passed down through generations, the virus replicated across multiple locations within chimpanzee DNA.

Methylation Suppresses LINC00662 in Chimpanzees

To regulate these viral invaders, the chimpanzee genome systematically shuts them down through a biological mechanism called methylation, which controls whether specific genes remain active or dormant.

In doing so, the retroviral insertions suppress the neighboring gene LINC00662 in chimpanzees. In contrast, the same gene remains active in humans and plays a significant role during early human brain development, according to Johan Jakobsson, professor of molecular neurogenetics at Lund University.

"The virus we investigated specifically affected chimpanzees," Jakobsson said. "But humans and chimpanzees have virtually the same gene set. Therefore, it is important to understand differences in how genes are regulated."

He added that understanding how gene regulation functions can help explain how it can either protect against or cause damage in contexts such as the brain.

Growing Three-Dimensional Brain Organoids

To observe the functional consequences of this viral insertion, the Lund University research team used stem cells derived from humans and chimpanzees to grow three-dimensional brain organoids. These miniature lab-grown models replicate key characteristics of early brain tissue development.

When analyzing the organoids, Patricia Gerdes, a postdoctoral researcher in molecular neurogenetics at Lund University, observed a stark contrast between the two species.

"The gene was strongly expressed in the human organoids, but not at all in the chimpanzees," Gerdes said.

CRISPR Tests Link Viral DNA to Gene Suppression

To test whether the retroviral insertion caused this suppression, the researchers used the CRISPR-Cas9 gene-editing tool to excise the viral DNA sequence from chimpanzee cells. Once the viral remnant was removed, LINC00662 resumed activity.

"This shows that the virus insertion is indeed behind the gene being switched off in the chimpanzee," Gerdes said.

When the researchers used CRISPR to artificially deactivate LINC00662 inside human brain organoids, the activity of other genes essential for neuron development and neural connectivity declined. The findings indicate that divergence between humans and chimpanzees stems not only from possessing different genes, but also from how existing genes are deployed.

Institutional Support and Funding

Funding for the research was provided by the Swedish Research Council (Vetenskapsrådet), the Swedish Brain Foundation (Hjärnfonden), the Swedish Childhood Cancer Fund (Barncancerfonden), and the European Union’s Horizon Europe research and innovation programme under Marie Skłodowska-Curie Actions.