Neil Shubin wrote the excellent book "Your Inner Fish: A Journey into the 3.5-Billion-Year History of the Human Body". At yesterday's Wall Street Journal he wrote the article "The Viruses That Shaped Our DNA."

Wall Street Journal

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ESSAY

The Viruses That Shaped Our DNA

Many of the traits that make these ultimate parasites so effective at transmitting diseases like Covid-19 also make them an essential part of our own genetic makeup.

By Neil Shubin

March 14, 2020

A virus is the stuff of mystery and fear, an invisibly lurking danger ready to spread explosively around the globe. The new coronavirus, like SARS, MERS and the seasonal flu, enters our bodies, finds its way inside our DNA and commandeers it to make more copies of itself. Viruses are, in many ways, the ultimate parasites.

Yet we, like every other creature on Earth, have a complex relationship with them. Many of the traits that make viruses so effective at transmitting disease also make them an essential part of our genetic makeup. As it turns out, their contributions to our genome over the eons account for a range of important human qualities.

Viruses sit at the edge of our definition of living things. They are tiny bits of genetic material enclosed by a protective shell. Alone, they sit lifeless and inert, waiting for a favorable environment in which to reproduce. Viruses are carried to their unwilling hosts by insects, droplets in the air, contact with infected surfaces and other mechanisms that bring cells of different species together.

When a virus encounters a host cell, a chain reaction of molecular events is set in motion: The virus attaches itself to the outer wall of the cell, enters inside, travels to the cell’s genome, merges with its genes and then tricks the host’s genome into making copies of itself.

The host cell becomes a factory for new viruses and can produce as many as a million of them before it dies. This explosive growth can happen simultaneously in tissues throughout the body. As the virus spreads in one individual’s body, it can escape via water droplets expelled from the air in the lungs, sweat produced by sweat glands or fluids produced by other organs, thereby passing the infection to others.

This selfish behavior makes viruses, as a Darwinian matter, enormously successful. There is an almost unfathomable number of them in and around us all the time. By some estimates, the number of viruses in the oceans alone is as large as a 10 with 31 zeros behind it. All told, there are more viruses on Earth than there are stars in the known universe.

What’s more, viruses are incredibly diverse and ever evolving. That is why we need a new flu vaccine each year and suffer from emerging diseases like Covid-19 with increasing regularity.

But researchers at the University of Utah came away with a different take on viruses while working in 2016 on a gene that plays a role in the ability to make memories. Mice with a mutation in this gene, known as Arc, can find their way through a maze with cheese in the center but—unlike mice with the normal Arc gene—can’t remember their path through the maze the next day. In humans, changes to Arc have been linked to a range of disorders, from schizophrenia to dementia. Arc is a gene that memories are made of.

To understand the gene, the team in Utah isolated the protein it made and put it under a powerful microscope. The lead researcher, Jason Shepherd, saw that the protein formed spheres that were visible at high magnification. That structure set off alarm bells for him: He was sure he had seen such spheres when he took a course in infectious diseases in his early days in graduate school. The Arc protein had spherules that looked exactly like those made by HIV, the virus that causes AIDS.

Dr. Shepherd gave the slide to viral specialists working in the building next door without telling them what was on it. The virus experts were sure they were looking at spheres made by HIV.

When the team sequenced the gene for Arc, decoding the string of molecules that make it up, they were in for an even bigger surprise. This memory gene was, for all purposes, a modified virus.

The virus that causes AIDS makes protein spheres because they protect HIV’s genes as they journey from cell to cell in its host. As it turns out, the same thing happens with the memory gene, Arc, which also works by moving genetic information from cell to cell. The viral strategy of making protein spheres, which is so dangerous in disease, works to our benefit in Arc.

Memory genes aren’t the only ones derived from viruses in our bodies. Genes that make proteins at work in the placenta, so essential for human reproduction, also arose from viruses. When a team from Germany did a computational search of the human genome, they found that as many as 85 genes derived from viruses may be at work in different parts of the brain and during pregnancy.

The past two decades have witnessed a golden age of genome projects. We have mapped the human genome, the corn genome and genomes for many thousands of species of microbes, fungi, animals and plants. With all this information, the more we look, the more we find ancient viruses hiding inside our genomes, as well as those of other creatures.

Almost 8% of the human genome is made up of viruses that once infected us but have been rendered inactive. That fact is even more astounding when you consider that genes—the part of DNA that codes for proteins—comprise only 2% of our genome. We have four times more viral genetic material inside our genome than our own genes.

Our genome is a graveyard for ancient viruses. Disabled viral fragments lie throughout; their wings have been clipped because they lack the sequences to jump from genome to genome. These viruses attacked our ancestors’ genomes eons ago, only to be disabled, and now lie as remnants of infections past. The memory gene Arc is a virus that long ago invaded, only to be put to work on an important bodily function. The tables were turned: The hacker, the invading parasite, was itself hacked to our benefit.

The ability to make spheres to move genetic material from cell to cell, so essential in the spread of infections such as AIDS, became useful to our distant ancestors. Researchers looking at the history of Arc have found that fish don’t have it, but their descendants—amphibians, reptiles, birds and mammals—do. The ancient fish that evolved to walk on land about 375 million years ago, it seems, got an infection that would change the course of history and, ultimately, our own abilities.

We live in a state of war between viral invaders and our own genome. One outcome can be that viruses take over and we become ill. The other is that viruses can be the source of new genetic inventions—fuel for evolutionary change.

Viruses are microscopic pieces of genetic material capable of wreaking havoc on our world and disrupting our interactions with one another. Yet new insights into genomes, and four billion years of the history of life, offer another side of the story. Each one of us is part virus, in ways that affect who we are and what we can do.

—Dr. Shubin is a professor of biology and anatomy at the University of Chicago. This essay is adapted from his new book “Some Assembly Required: Decoding 4 Billion Years of Life Using Ancient Fossils and DNA,” which Pantheon will publish on March 17, 2020.