What Percent Virus Are You?

With advances in genome sequencing and computational tools to analyze genomic information, researchers are able to estimate that about 8 percent of the human genome is made of sequences that originated as invasive retroviruses. To put that number in perspective, genes make up about 1 percent to 1.5 percent of your genome.
Hannah Moots
December 14, 2016

The more scientists look for viruses, the clearer it becomes that they exist nearly everywhere — a drop1 of surface seawater typically contains about 10 million of them. Viruses are found across the globe — on land, in oceans, and in a variety of host organisms, from bacteria to plants and animals. And that includes humans, down to our genetic building blocks.

Since viruses cannot replicate on their own, they use the cells of the organisms they infect to make new copies of themselves. One type of virus, retroviruses, inserts a DNA copy of its RNA sequence into the host cell’s genome upon infection. If the virus inserts into a reproductive cell and that cell goes on to produce an offspring, the viral DNA gets passed on from parent to child as part of the genome.2 At this point, the virus is locked in and is passed on from generation to generation. These are called endogenous retroviruses, or ERVs, and this can happen in any type of organism that viruses infect, including humans.

So yes, that means your genome is part virus. More than 100,000 sequences in the human genome3 originated this way. Scientists have recognized the presence of viral DNA in the human genome for decades, but it wasn’t until after the human genome was sequenced, or mapped, in 2003 that they could study just how much of our DNA comes from viruses. While the viral sequences in the human genome today originated from about 50 infection events in the distant past that were passed on as described above, the viral sequences were copied and reinserted hundreds, sometimes thousands, of times.

With advances in genome sequencing and computational tools to analyze genomic information, researchers are able to estimate that about 8 percent of the human genome is made of sequences that originated as invasive retroviruses. To put that number in perspective, genes4 make up about 1 percent to 1.5 percent of your genome.

Scientists have calculated this by looking for similarities between sequences in our genome and free-living viruses, such as common cold viruses or mononucleosis. By placing ERVs into an evolutionary tree of viruses, they can even extrapolate from what type of virus each sequence originated. And they’re starting to realize how important that DNA might be to genome function.

Although they were once thought to be simple traces of past viral infections, it turns out that these viral sequences can affect the host. At first, the sequences may still produce new viruses, which could infect other cells or other hosts. And when they insert into a genome, they can disrupt the function of that region of DNA. Our genome has a number of ways of combating and silencing these invaders, however. When that happens, these sequences aren’t harmful anymore but are still scattered throughout the genome. Harmit Malik, evolutionary biologist at the Fred Hutchinson Cancer, said that “once they’ve been ‘domesticated’ then the genes or protein products that they encode might be of value to the host.”

This allows the host to use a genomic sequence that was evolved by the virus for other purposes. Although the viral DNA started as a parasitic element, in some cases it has been co-opted into functional roles by our genome, explained Joanna Wysocka, developmental biologist at Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. Wysocka researches the role that ERVs play in stem cells developing into specific types of tissue cells.

In fact, scientists think endogenous retroviruses have been essential for the evolutionary development of placental mammals. While mammals’ closest relatives — reptiles — lay eggs, most mammals give birth to live young. In reptiles, the developing embryo has only the nutrients provided in the egg; there is no way to pass nutrients from parent to embryo after fertilization. In placental mammals, however, nutrients can be passed from the mother to the developing embryo throughout gestation. This is more energy-efficient than the reptilian strategy in which large amounts of nutrients are invested in eggs that may not be fertilized.

As is the case with many evolutionary benchmarks, this comes with a trade-off. One challenge for mammals is the mother’s immune system. Designed to identify and protect the body from foreign bacteria, viruses and other invaders, a mother’s immune system might see an embryo as foreign because its genetic makeup is different from hers. Scientists now think that placental mammals co-opted a gene designed to allow retroviruses to evade the host’s immune system, to cloak a developing embryo from the mother’s immune system. “Obtaining nutrients through cell-cell fusion and evading the host’s immune system are properties that viruses are very good at, and both have been usurped into biological processes for us,” Malik said. In humans, a retroviral sequence known as ERVWE1 produces a protein called syncytin in the placenta, which allows nutrients to pass from mother to fetus, a skill that mammals have and our egg-laying ancestors did not. We can thank the co-option of viral DNA.

These endogenous retroviruses are sometimes talked about as “fossils” — relics of ancient times — and while it is true that many entered the human genome long ago, the term “fossil” conveys the image of something static, unchanging and inactive: a fly trapped in amber or a trilobite cemented in sandstone for thousands or millions of years. But recent research is showing that sometimes sequences originating from viral infections are active in the genome, at times being changed and changing the genome itself. Some seem to have little to no effect on their host, while others can be deleterious and some have been co-opted into functional roles.

Even when the traces of viral infections past aren’t serving a functional role in the genome, they may serve as an important source of variation in our species. They are tools that could be put to use by the genome if the right problem arose.

“Our evolutionary history of viral infections has affected how we’ve been able to evolve,” Wysocka said. “It has provided raw material for evolution in the future.”

Hannah Moots is a Ph.D. student researching health and disease in the archaeological record. She is based in Palo Alto, California.

December 25, 2016