Ancient Viral DNA in Chimpanzee Genome May Explain Brain Differences with Humans

Viruses may be minuscule, but one could have influenced major differences between human and chimpanzee brains.

Millions of years ago, a virus left DNA behind in an African ape’s genome, and the genetic material persisted in modern-day chimpanzees. These remnants of ancient infections appear to influence genes involved in neuron development, potentially helping to explain how human and chimpanzee brains diverged so significantly, according to research published October 23 in Science Advances.

Human brains are three times larger and more cognitively powerful than those of chimpanzees, yet the protein-coding genes in both species are remarkably similar. Faced with this puzzle, researchers turned to the regulatory regions of the genome—segments that control when and where genes are activated or silenced.

Changes in gene regulation can arise from viruses. Retroviruses insert their own DNA into host genomes to replicate, and sometimes these parasitic sequences become permanently integrated into reproductive cells, passing down through generations. Though these endogenous retroviruses can no longer produce infectious viruses, they can exert profound biological effects, especially when they amplify across the genome. Indeed, such viral remnants constitute at least 8 percent of both human and chimpanzee genomes and have been linked to major evolutionary milestones, such as the development of the mammalian placenta.

Johan Jakobsson, a neuroscientist at Lund University in Sweden, and his colleagues focused on a specific viral footprint in chimpanzees. The insertion originated from an infection in an ancestral African ape roughly 5 to 7 million years ago. In chimpanzees, the viral DNA integrated into 158 distinct locations in the genome, but it is conspicuously absent in humans. The reasons for this discrepancy remain unknown.

To investigate how this viral signature might affect chimpanzee brains, the researchers used CRISPR gene-editing technology to remove the viral DNA from chimpanzee stem cells. Once the viral sequence was excised, a nearby gene called LINC00662—typically silenced in chimpanzee brain cells—became active. This mirrors the normal state of human brain cells, where LINC00662 is expressed. The team further confirmed the link by using CRISPR to suppress LINC00662 in human cells, mimicking the silenced condition seen in chimpanzees.

When LINC00662 was active in either chimp or human cells, the researchers observed increased activity in other genes critical for brain development, including those involved in neuronal maturation and the formation of new neural connections. While the exact impact on chimpanzee brain biology is not yet clear, Jakobsson suggests this regulatory difference may have contributed to the evolutionary divergence of human and chimpanzee brains. “Our findings show one way an ancient viral DNA insertion could create a lasting difference in how a gene is regulated in humans and chimpanzees,” he notes.

Other scientists emphasize the broader significance of the study. Giorgia Modenini, an evolutionary biologist at the University of Padua, explains that while previous research has focused on single-letter DNA changes, this work highlights how organisms accumulate genome alterations through other mechanisms. Ravinder Kanda, an evolutionary geneticist at Oxford Brookes University, praises the study for convincingly demonstrating that viral remnants influence developmental differences between human and chimp neurons. However, he cautions that this may represent only a fraction of the viral holdovers shaping brain evolution. “I think there are many, many more retroviruses to be discovered, and at the moment we’ve only touched the tip of the iceberg,” Kanda says.

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