It is easy to think of viruses as nothing more than tiny invaders that make us sick, but their influence stretches far beyond colds, fevers, and global pandemics. Today’s viruses are busy hijacking our cells to copy themselves, but some viruses from millions of years ago left behind an even stranger legacy: their DNA is still tucked inside our genomes. Now, scientists have discovered that one such ancient viral leftover may have helped shape the most fascinating organ in the natural world—the brain. A team of researchers reported in Science Advances that a piece of viral DNA, present in chimpanzees but mysteriously absent in humans, appears to act as a genetic switch that silences a gene important in brain development. That tiny difference, they argue, could help explain why human and chimpanzee brains ended up so different, despite the fact that our two species share almost identical protein-coding genes. Humans and chimps look nothing alike when you peer inside their skulls: the human brain is roughly three times larger and far more cognitively powerful. Yet, as neuroscientist Johan Jakobsson of Lund University in Sweden points out, “most of their protein-making genes are very similar.” So if the genes themselves are nearly the same, what accounts for such a dramatic difference in brainpower? The answer, Jakobsson and his colleagues suspected, lies not in the genes themselves but in the parts of the genome that decide when and where those genes are switched on or off. And that, it turns out, is where viruses come in.
To understand how a virus could shape evolution, it helps to know a little about a strange class of viruses called retroviruses. These viruses are like genetic parasites: they insert their own DNA directly into the genome of the host cell, essentially commandeering the cell’s machinery to produce more viruses. But this genetic hijacking doesn’t always stop when the infection ends. Sometimes the viral DNA stays behind long after the virus itself is gone, becoming a permanent fixture in the host’s DNA. If that insertion happens in reproductive cells—sperm or eggs—the viral DNA can be passed down to future generations. Over time, these leftovers, known as endogenous retroviruses, accumulate in a species’ genome. They no longer produce infectious viruses; many are broken, silenced, or co-opted, but they still take up space and can influence the host’s biology in surprising ways. Scientists have known for years that these ancient viral remnants are astonishingly abundant. In both humans and chimpanzees, they make up at least 8 percent of the genome—far more than the DNA that codes for proteins. Some of these viral fossils have been linked to major evolutionary innovations, including the evolution of the placenta in mammals. But their role in brain evolution has remained more mysterious. Jakobsson and his colleagues focused on a particular viral vestige found in chimpanzees but not in humans. This relative of the modern retrovirus infected an ancestral African ape somewhere between 5 million and 7 million years ago, just around the time that the ancestors of humans and chimpanzees were going their separate evolutionary ways. In modern chimpanzees, that ancient virus’s DNA has multiplied and moved, leaving copies of itself scattered at 158 different locations across the genome. In humans, however, it is completely absent. No one knows exactly why—maybe humans lost it, maybe the infection never happened in human ancestors, or maybe something else erased it from our lineage. But the absence is striking, and it made the viral remnant a perfect candidate for explaining some of the regulatory differences between our species.
To see what that viral DNA actually does, the researchers needed to dig deep into the genome and watch its effects. They started with stem cells from chimpanzees, which have the potential to develop into many different cell types, including brain cells. Using CRISPR, a gene-editing tool that allows scientists to make precise cuts in DNA, they carefully removed the viral DNA from the chimpanzee cells. The result was immediate and revealing. Near the spot where the viral DNA had been removed, a gene called LINC00662 suddenly switched on, producing RNA that the team could detect. In normal chimpanzee cells, LINC00662 is usually silenced, quiet, dormant. But once the viral DNA was removed, it woke up. This, the researchers realized, was exactly the pattern seen in human cells, where LINC00662 is active. In other words, the viral DNA wasn’t just sitting there passively; it was actively turning off a gene that, in humans, is allowed to do its job. To confirm their findings, the researchers did the reverse experiment in human cells. They used CRISPR to shut off LINC00662, mimicking the silenced state found in chimpanzees. Together, the two experiments showed that the ancient viral DNA is directly responsible for the difference in LINC00662 activity between humans and chimpanzees. It was as if the viral remnant were acting as a light switch, flicking the gene off in chimps while leaving it on in humans. The gene itself isn’t a protein-making gene in the traditional sense; it’s what scientists call a long non-coding RNA, a molecule that doesn’t code for proteins but instead helps regulate other genes. That makes it all the more interesting, because it suggests the viral DNA is not just changing one protein but potentially altering an entire network of genetic activity.
The implications of that single genetic switch become clearer when you look at what LINC00662 does. When the researchers allowed LINC00662 to be active in either chimpanzee or human cells, they noticed something remarkable: other genes began to show increased activity too, particularly genes involved in brain development. These included genes important for the development and maturation of neurons and for building the connections—synapses—that allow brain cells to communicate. In other words, flipping LINC00662 on seemed to spark a cascade of activity in a whole network of genes related to making and wiring brain cells. That suggests the ancient viral DNA in chimpanzees may have silenced not just one gene but an entire suite of genes involved in building a brain. But what does that mean for the actual differences between human and chimpanzee brains? It’s still not entirely clear, Jakobsson says. The researchers can’t yet say exactly how shutting down this gene network changed the biology of chimpanzee brains. But the discovery offers a compelling glimpse into one way an ancient viral insertion could create a lasting difference in gene regulation between two closely related species. “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,” Jakobsson says. It’s possible that this difference helped shape the evolutionary path that led to humans’ unusually large and cognitively powerful brains. But there are likely many other genetic and environmental changes also involved in the puzzle. Evolution is rarely simple, and the story of how human and chimpanzee brains diverged is probably the result of countless small changes, some in genes, some in gene regulation, and some in the environment. Still, the idea that a virus from millions of years ago could be one of those changes is a powerful reminder of how strange and interconnected the history of life really is.
Other scientists are taking note. Traditionally, researchers looking for the genetic basis of human brain evolution have focused on single-letter changes in DNA—the tiny mutations that alter a gene’s code. But this new study highlights that evolution can work through much larger, messier changes as well. Giorgia Modenini, an evolutionary biologist at the University of Padua in Italy, who was not involved in the research, says the study is a valuable reminder that organisms can rack up genome changes in ways beyond simple point mutations. Ravinder Kanda, an evolutionary geneticist at Oxford Brookes University in England, was similarly impressed. She says the researchers did a convincing job of showing that these particular viral leftovers influence developmental differences between human and chimpanzee neurons. “They’ve proved that absolutely,” she says. But she cautions that it’s hard to say just how much this single viral element matters in the grand scheme of brain evolution. “How far that goes, I don’t think we can quite say yet.” There could be other regulatory mechanisms at work, or this ancient viral remnant might be just one small piece of a much larger puzzle. Kanda suspects there are many more endogenous retroviruses waiting to be discovered, each with its own potential to shape gene activity and development. “I think there are many, many more retroviruses to be discovered, and at the moment we’ve only touched the tip of the iceberg,” she says. The genome, it turns out, is less like a neatly organized instruction manual and more like a palimpsest—a manuscript written, erased, and overwritten over millions of years, with ancient viral scribbles still visible beneath the modern text.
For those of us who don’t study genomes, all of this can feel wonderfully strange. It’s almost poetic to think that the very thing that makes us human—our big, creative, powerful brain—might have been shaped in part by an ancient viral infection that our ancestors escaped or erased. The chimpanzee genome carries the fossil of that infection, a ghostly remnant that still reaches out from millions of years ago to silence genes involved in building neurons. Humans, for reasons unknown, don’t have that ghost. Instead, the gene LINC00662 remains active in our brain cells, and with it, a network of genes that help neurons grow, mature, and connect. Whether that is the reason we can write symphonies, build spacecraft, and ponder our own origins is still an open question. But the research adds to a growing understanding that our genome is not a pristine, sacred text handed down intact from our distant ancestors. It is a living record of every infection, every struggle, every twist of evolutionary fate. Viruses may be minuscule, but they have left enormous footprints in the story of life. And sometimes, those footprints lead all the way up to the human mind itself. This is just one study, and scientists will need many more experiments to understand exactly how viral DNA influences brain function and evolution. But it’s a thrilling reminder that the past is never really past. It lives on inside our cells, in the molecular fossils of infections that happened millions of years ago. The next time you think about what makes human brains special, you might want to thank an ancient virus—or, more precisely, the luck of not inheriting one.
