The Viruses That Shaped Our DNA

The Viruses That Shaped Our DNA Many of the traits that make these ultimate parasites so effective at trans mitting diseases like Covid-19 also make them an essential part of our own genetic makeup By Neil Shubin, Mar 14, 2020, Wall St. Journal
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, ME RS and the seasonal flu, enters our bodies, finds its way inside our DNA an d 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 wit h them. Many of the traits that make viruses so effective at transmitting d isease 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 b its of genetic material enclosed by a protective shell. Alone, they sit lif eless and inert, waiting for a favorable environment in which to reproduce. Viruses are carried to their unwilling hosts by insects, droplets in the a ir, 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 i s set in motion: The virus attaches itself to the outer wall of the cell, e nters inside, travels to the cell’s genome, merges with its genes a nd 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 simultan eously in tissues throughout the body. As the virus spreads in one individu al’s body, it can escape via water droplets expelled from the air i n the lungs, sweat produced by sweat glands or fluids produced by other org ans, thereby passing the infection to others.
This selfish behavior makes viruses, as a Darwinian matter, enormously succ essful. 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 diseas es like Covid-19 with increasing regularity.
But researchers at the University of Utah came away with a different take o n 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 ran ge of disorders, from schizophrenia to dementia. Arc is a gene that memorie s are made of.
To understand the gene, the team in Utah isolated the protein it made and p ut it under a powerful microscope. The lead researcher, Jason Shepherd, saw that the protein formed spheres that were visible at high magnification. T hat structure set off alarm bells for him: He was sure he had seen such sph eres when he took a course in infectious diseases in his early days in grad uate school. The Arc protein had spherules that looked exactly like those m ade by HIV, the virus that causes AIDS. ===========Dr. Shepherd gave the slide to viral specialists working in the building ne xt door without telling them what was on it. The virus experts were sure th ey 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 bodie s. 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 comp utational search of the human genome, they found that as many as 85 genes d erived from viruses may be at work in different parts of the brain and duri ng pregnancy.
The past two decades have witnessed a golden age of genome projects. We hav e mapped the human genome, the corn genome and genomes for many thousands o f species of microbes, fungi, animals and plants. With all this information , the more we look, the more we find ancient viruses hiding inside our geno mes, as well as those of other creatures.
Almost 8% of the human genome is made up of viruses that once infected us b ut 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 ma terial 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 infec tions past. The memory gene Arc is a virus that long ago invaded, only to b e 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 di stant ancestors. Researchers looking at the history of Arc have found that fish don’t have it, but their descendants—amphibians, repti les, 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 ch ange the course of history and, ultimately, our own abilities.
We live in a state of war between viral invaders and our own genome. One ou tcome can be that viruses take over and we become ill. The other is that vi ruses can be the source of new genetic inventions—fuel for evolutio nary change.
Viruses are microscopic pieces of genetic material capable of wreaking havo c on our world and disrupting our interactions with one another. Yet new in sights into genomes, and four billion years of the history of life, offer a nother 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.
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