The Human Genome Is Full of Viruses

Ben L. Callif

Your body requires viruses, but viruses don’t always require a body

Ben L. Callif

Viruses use cellular mechanisms of transcription and translation (turning DNA to RNA and RNA to proteins) to replicate themselves and infect all kinds of living things. Image Credit: Arizona State University

Viruses are amazing molecular machines that are much tinier than even the smallest cells. We often think of viruses like the flu, chickenpox, or herpes as “external” invaders, but viruses are more inherently associated with human life than we often realize. Even after recovering from an infection there will always be a piece of that virus encoded within your DNA. Approximately 8% of the human genome is made up of endogenous retroviruses (ERVs), which are viral gene sequences that have become a permanent part of the human lineage after they infected our ancient ancestors. And these endogenous retroviruses don’t just sit silently in the genome — their expression has been implicated in diseases like autoimmune disorders and breast cancer.

But endogenous retroviruses don’t only harm our health; they can also be extremely useful for human survival. For example, they play a very important role as an interface between a pregnant mother and her fetus by regulating placental development and function. It has been suggested that viruses are not only necessary for the existence of placental mammals, but also for the existence of life in general. Professor Luis P. Villarreal, the Founding Director of the Center for Virus Research at UC Irvine, says it like this: “So powerful and ancient are viruses, that I would summarize their role in life as ‘Ex Virus Omnia’ (from virus everything).”

Viruses are powerful, ancient, and vital to our existence, but they are extremely simple constructions. They tend to be nothing more than a few pieces: a protein capsid, which is a simplistic and protective shell; a protein called a polymerase, which carries out most of the functions related to replicating the viral genome; and a sequence of nucleotides — either RNA or DNA — that encode for the previously mentioned viral proteins. The image below shows one of the ways that these viral components can be assembled into a unified whole. Unlike a human genome, a viral genome can be thought of as a self-contained model of the entire viral form. Within its RNA or DNA, a virus contains all the instructions necessary to create an entirely new body for itself and to replicate those same instructions. The simplicity and self-contained nature of viruses makes them phenomenal tools for biological engineering and medicine.

Viruses (specifically bacteriophages) as imaged with an electron microscope. Image Credit: Wikimedia Commons

Viruses are so simple that they don’t always need their own body to survive; they have circadian rhythms like all living things. We experience these rhythms through cycles of sleep and wakefulness, whereas viral rhythms occur as periods of dormancy between rounds of infection. Viruses don’t technically have a body during their dormant phase — they are nothing more than a string of letters in the book of the genome. But, as soon as something disturbs their sleep (like a mutation or a new virus invading the host) viruses can awaken and rebuild their physical bodies from a purely genetic form. When the wrong (or right, depending on your perspective) protein manages to leak out of a dormant viral gene, it is like the virus is suddenly awake again. A new physical body means that it has all the tools necessary to replicate.

Even beyond these rhythmic cycles, certain kinds of viruses don’t need a physical form at all. These disembodied viruses are called transposable elements, or transposons. True viruses have a body made from proteins, but transposons are mobile genetic elements — sequences of DNA that physically move in and out of genomes. For this reason, they are often referred to as “jumping genes.” Transposons do very much the same thing as true viruses, i.e. they copy and paste themselves throughout genomes. They are so similar to true viruses that some endogenous retroviruses (ERVs) are themselves transposons. As stated above, ~8% of the human genome is made up of ERVs, but nearly 50% of the human genome is made of transposons! Humans are basically just big piles of viral-like sequences.

Transposable elements (transposons) are sequences of DNA that literally jump in and out of the genome. Image Credit: Harvard University

Transposons have a disturbing capacity to disrupt important genes by inserting themselves into the DNA sequences. It’s like if a series of words in a book could physically move around from page to page — these words would have a high likelihood of jumping into the middle of a sentence, thereby making it nonsensical. Amazingly, transposons preferentially insert themselves into important and functional genes — as if those jumping words wanted to disrupt the most interesting parts of the book rather than the index or bibliography. This is a powerful evolutionary strategy, since transposons are much more likely to get “read” by a cell if they jump into the middle of an important (and therefore, active) gene.

Transposons can very easily mess up important genes that we need to survive, so it has been theorized that epigenetic mechanisms evolved to stop transposons from moving around the genome. Furthermore, since transposons can rapidly alter DNA sequences, they are thought to play a major role in the processes of evolution and speciation (how a species evolves into a new form). In plants, transposons become highly active in response to stressful conditions, and this could act as a rapid source of short-term mutation when the environment starts pressuring you to survive or die. In addition, an animal’s genome changes when they are domesticated (like going from a wolf to a dog, or from an aurochs to a cow), and a majority of these changes occur in transposon sequences. No one is really sure why or how this happens, but it is clear that viruses play a very important role in rapid genetic change.

A biological virus (whether it is a true virus, an endogenous retrovirus, or a transposon) can literally lay dormant in a word document as a string of As, Ts, Cs, and Gs. In other words, viruses can exist independently of genetics, solely in the symbolic dimension of evolution. A virus is nothing more than an idea until it finds a host within which it can replicate itself. Despite their ephemerality, viral sequences are clearly important for our lives as humans. After all, they compose nearly half of our genome and seem to play an important role in our long-term evolution.

In many ways, viruses are eerily reminiscent of the idea of ancient spells, which sit quietly as words in a book until someone utters the mystical syllables and unleashes the magic contained within. Perhaps due to the mysticism of this concept, many scientists and philosophers have a hard time accepting viruses as living things. But, whether or not you classify viruses as living entities, they certainly show us that the line between living things and pure information is a lot fuzzier than we often think…

If you enjoyed this read, sign up for our mailing list to stay connected!