An Ancient Virus Left Its Mark on Chimpanzee DNA Even After Millions of Years and May Have Helped Shape Human Brain Evolution

Millions of years after an infection, viral DNA still influences how developing chimpanzee brain cells behave.

Millions of years ago, a virus infected the ancestors of chimpanzees and left behind a genetic souvenir. Humans never inherited it. And that twist of evolutionary fate may have helped send our brains down very different paths.

The ancient virus itself is long extinct, but its genetic sequence is still at work. Scientists have discovered that a fragment buried in chimpanzee chromosomes switches off a gene involved in the growth and maturation of brain cells. When researchers removed the viral DNA using the gene-editing tool CRISPR, the gene sprang back to life.

Could this ancient, yet still lingering primate infection explain why humans developed brains three times larger than those of our closest living relatives, despite sharing so much of our genetic code? It’s a stretch, but the science is fascinating.

The Infectious Genetics Inside a Chimpanzee Chromosome

Retroviruses can insert copies of their genetic material into a host’s DNA. When such insertions reach cells that give rise to eggs or sperm, descendants can even inherit them. An infection can thus, in some cases, become a permanent feature of a species’ genome.

These ancient viral fossils account for at least 8 percent of human and chimpanzee DNA. One family, called PTERV1, is particularly puzzling. Researchers identified 158 insertions in the chimpanzee reference genome. Related remnants also occur in bonobos and gorillas, yet humans lack them.

Scientists believe this family of viruses first infected African apes around 5 to 7 million years ago. But the particular piece of viral DNA that silences the brain-related gene arrived later, sometime between 1.5 and 5 million years ago. By then, the ancestors of humans and chimpanzees had already gone their separate evolutionary ways. The viral DNA became embedded in the lineage that eventually gave rise to modern chimpanzees and bonobos, which explains why both species carry it while humans do not.

Why did our lineage end up without these insertions? The ancestors of humans and other African apes might have lived in different places, sheltered by the retrovirus outbreak that affected other primates. Or perhaps our human ancestors might have possessed antiviral defenses that blocked their inheritance. A human antiviral protein, TRIM5α, blocks PTERV1 in laboratory tests, so the latter explanation checks out.

To investigate what the leftovers do, Patricia Gerdes and colleagues at Lund University in Sweden grew tiny, three-dimensional models of developing brains from human and chimpanzee stem cells. These brain organoids model selected stages of nerve-cell development.

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One difference stood out. A region on chimpanzee chromosome 19 contained a roughly 7,000-letter PTERV1 insertion within a gene called LINC00662. The gene was active in human organoids but silent in chimpanzee models.

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“The gene was strongly expressed in the human organoids, but not at all in the chimpanzee organoids,” Gerdes said in a press statement from Lund University.

Switching Off a Gene Without Changing Its Code

The researchers found that chimpanzee cells had placed chemical marks, known as DNA methylation, over the viral insertion and surrounding DNA. Cells use such marks to suppress troublesome genetic sequences. Here, that protective response appeared to spread into the neighboring gene, silencing it too.

Then came the decisive experiment. Using CRISPR gene editing, the team removed the viral segment from chimpanzee stem cells. LINC00662 began producing RNA again.

“This shows that it is in fact the viral insertion that is responsible for the gene being switched off in chimpanzees,” Gerdes said.

What does the gene do? LINC00662 produces a long RNA molecule that appears to interact with proteins involved in building the internal scaffolding of developing neurons. Human fetal brain data show that its activity peaks 10 to 12 weeks after conception.

When the researchers suppressed LINC00662 in human organoids, the organoids still formed and maintained broadly similar mixtures of cells. But by day 30, developing neurons showed reduced staining for a structural protein associated with the extensions that become axons and dendrites — the branching cables through which neurons send and receive signals.

Curiously, several genes involved in growing these extensions became more active, perhaps because cells were attempting to compensate, although this explanation remains untested.

One Piece of a Much Larger Evolutionary Puzzle

Although it seems far-fetched that viral infections could have such an outsized effect on different lineages of our ancestors, the findings build on 2021 organoid research suggesting that a delay in a developmental cell-shape transition helped human brains expand. A 2022 study linked another stretch of noncoding DNA to differences in human and chimpanzee brain development.

Evolution can reshape brains by changing when genes operate, not just by changing the proteins they make, and scientists are only recently beginning to disentangle the ramifications across deep time.

To be sure, these experiments cannot establish whether this ancient infection changed chimpanzee intelligence, human brain size or the evolutionary split itself. Organoids reproduce only fragments of early brain development and they’re imperfect by their very nature. Nor have researchers tested its restoration in a developing chimpanzee brain.

Still, the results are deeply fascinating. They remind us that viruses do not merely make organisms sick. Sometimes they leave behind changes that evolution carries for millions of years — including, perhaps, subtle differences in the way brains are built.

The new findings appeared in the journal Science Advances.