We are all familiar with viruses like the coronavirus, Zika virus, Ebola, and the flu, which have troubled humanity for years. However, what is truly astonishing is that viruses, over millions of years, have not only caused diseases but have also influenced human evolution. Some even speculate that human life itself may have emerged from the accidental fusion of viral genes.
Viruses have a simple structure: a strand of genetic material wrapped in a protein coat. Once a virus infects a cell, it hijacks the cell’s machinery to replicate its genes and produce new viruses, which then go on to infect more cells.
For most viruses, like the flu, the process ends there. But some retroviruses, including HIV, are sneakier—they can insert their genetic material directly into our DNA. Once in, the virus lies dormant, only reactivating when the immune system is weakened, and begins making new viruses.
However, once retroviruses insert themselves into an organism’s DNA, they can’t always remain unchanged. The embedded viral genes are still readable and can be copied, eventually being inserted into different parts of the genome. Over millions of years, these viral DNA sequences mutate randomly and lose the ability to exit the host cell, becoming stuck inside the genome. If these events occur in reproductive cells—eggs and sperm—these viral sequences are passed down through generations and become permanent fixtures of the genome.
In fact, about half of the human genome is made up of DNA sequences that trace back to long-dead viruses or "jumping genes"—transposable elements. Some researchers even estimate that the number could be as high as 80%, as many ancient sequences have degenerated beyond recognition.
Over time, large chunks of repetitive viral-derived DNA have spread throughout the human genome. Some of this may be genetic "junk," but closer inspection has revealed that certain embedded viral genes have actually been tamed by our bodies or even played a role in human evolution.
Around 15 years ago, researchers in the U.S. discovered a human gene called syncytin that is active only in the placenta. This gene produces a protein that helps fuse placenta cells together, forming the trophoblast layer, which provides nutrients and protection to the developing embryo. Strangely, the syncytin gene looks a lot like the gene of a retrovirus.
Further research revealed another syncytin gene involved in forming the placenta and preventing the mother’s immune system from attacking the fetus. This gene also appears to come from a retrovirus. Currently, both humans and other great apes possess two syncytin genes. While mice have two similar genes with the same function, they seem to originate from completely different viruses. Cats and dogs also have syncytin genes from other virus types.
Interestingly, pigs and horses lack any viral-derived syncytin genes and do not have a trophoblast layer. This suggests that mammals with syncytin genes were infected by specific viruses millions of years ago. Over time, these viruses played a crucial role in the development of the placenta, becoming permanent parts of the genome.
The syncytin example illustrates how viruses can influence the genetic activity of their hosts, and there are many more such cases, even involving ancient viral sequences.
In 2016, scientists from the University of Utah discovered that an endogenous retrovirus from 45-60 million years ago, which infected our ancestors, can activate the AIM2 gene in response to a signal that the body is under viral attack. This triggers infected cells to self-destruct to prevent the infection from spreading.
These ancient viruses have become "double agents" that help our cells fight off new viral invaders.
Another viral influence on our evolution is near the PRODH gene, which is important for brain function, especially in the hippocampus. In humans, this gene is activated by an extinct retrovirus. Chimps also have a version of the PRODH gene, but it’s less active in their brains.
This suggests that millions of years ago, a virus inserted itself next to the PRODH gene in our ancestors, but this did not happen in the evolutionary lineage of chimps. Today, defects in PRODH are linked to certain brain diseases.
Remarkably, some studies suggest that viruses have played a role in the evolution of human intelligence. All land animals, including humans, possess the Arc gene, which controls the formation of synapses in the brain. This gene is responsible for cognitive abilities and learning behaviors. Defects in the Arc gene can cause developmental brain disorders, such as autism. Mice lacking Arc cannot learn new things, and if the Arc gene is removed from them, they forget everything.
In 2018, a study published in Cell revealed that the Arc gene traces its origins to a retrovirus. The researchers found that Arc is a descendant of the Gag gene, a retroviral gene that has been co-opted through evolution to facilitate communication between brain cells.
The study also found that Arc is found exclusively in the brains of land animals and not in marine animals. One possible explanation is that, as marine animals adapted to land, they were infected by retroviruses that helped them evolve smarter brains suited for the new environment.
Interestingly, the way Arc functions in the brain is similar to how viruses infect cells. Arc forms a protective shell, "infecting" neurons with the instruction to form synapses. When researchers first examined images of Arc, they thought it resembled the HIV virus infecting cells.
This discovery was supported by an independent study published in Cell at the same time.
These findings not only provide critical insights into human evolution but also open new avenues for treating brain diseases. For example, enhancing the activity of the Arc gene in the brain might reverse memory loss.
While it has long been recognized that viruses influence the evolution of their hosts, most known endogenous viral elements consist of small gene fragments. However, a new study published in Nature on November 18th reveals that the genomes of some giant viruses—large double-stranded DNA viruses—can be fully integrated into their hosts' genomes. Unlike smaller viral DNA fragments, these giant viruses contribute large numbers of base pairs to the host genome, expanding our understanding of how viruses shape eukaryotic evolution.
Giant viruses, which are about 10 times larger than typical viruses, challenge traditional virus biology. In addition to their enormous size, their genomes sometimes contain genetic material from bacteria and eukaryotic organisms, including metabolic genes. Because of this, their genomes don’t always look like those of viruses.
Researchers have identified 18 examples of giant endogenous viral elements (GEVEs) across various host genomes. In two samples, the entire viral genome seems to have integrated into the genomes of plankton, making up as much as 10% of the host genome. Overall, these GEVEs contributed between 78 and 1,782 genes.
This research suggests that the integration of giant viruses into host genomes may be more common than previously thought, and these viruses could be a previously overlooked source of genetic diversity in eukaryotes.
What helps the human body "tame" viruses? Researchers have identified a special group of proteins called KRAB zinc finger proteins (KRAB ZFPs). These proteins are able to capture viral sequences in the genome and "anchor" them in place.
More than 300 different KRAB ZFPs have been found in the human genome, each targeting different viral DNA. These KRAB ZFPs act as "killers" of endogenous retroviruses, but more importantly, they "develop" these viral elements, allowing organisms to adapt and use them for beneficial purposes. This reshuffling of the genome creates new genetic variation, providing raw material for natural selection.
The studies above show that the viruses embedded in our genomes have played a significant role in human evolution. But this doesn’t mean viral infections are always beneficial. Countless examples show that viral infections can lead to death, such as the ongoing COVID-19 pandemic.
There is also increasing evidence that jumping transposons (a type of viral gene) can cause genetic chaos in cancer cells. Studies have shown that brain cells are particularly receptive to reactivating these jumping genes, which could increase neural diversity and enhance brain function but may also contribute to age-related memory problems or disorders like schizophrenia.
So, are these viruses in our DNA our friends or enemies? The answer is both. In the short term, they may have negative effects, making them "enemies" in the context of individual lifespan. But over time, these viral elements have become a powerful force in evolution, helping humans adapt to environmental changes—making them ultimately our "friends."
Viruses that infect humans today, like HIV, may also influence our evolution in the future, but it may take many generations before we realize the long-term impact.
