Viruses: The Original Genome Editors

 

Viruses stealthily spread among us, commandeering our very cells and waging a relentless war with our immune systems. You know them for everything from the common cold and flu to catastrophic outbreaks of HIV and Ebola. At the very least, they’ve probably ruined your plans once or twice. But did you know that a significant portion of your DNA actually originated from viruses?

 

Most of us think that the human genome is just that — human. However, scientists estimate that approximately 8% of our genome can actually be traced back to viruses. Viruses infect organisms, or hosts, from all domains of life, and sometimes viral genomes become incorporated into the host DNA during an infection.

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Karyotype of the chromosomes that make up the human genome, 8% of which is viral in origin. Image credit: Doc. RNDr. Josef Reischig, CSc. via Wikimedia Commons. Licensed under CC BY-SA 3.0.

 

 

But is our 8% viral DNA actually doing anything, or is it simply a functionless molecular scar left over from ancient infections? More broadly, how might this have impacted the evolution of life on earth? To answer these questions, we can look at examples from two branches of the tree of life that diverged eons ago: bacteria and mammals.

 

A Micro Perspective

Bacteria and their viruses (known as bacteriophages, or phages), have a complicated relationship. Some infectious phages invade bacterial cells, take over the host’s molecular machinery, and use it to make hundreds of copies of themselves before killing the cell and moving on to the next host. Obviously, this is not a preferred outcome for the bacteria. But some phages utilize a sneakier strategy for replication.

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Transmission electron micrograph of bacteriophages attached to a bacterial cell wall. Image credit: Dr Graham Beards via Wikimedia Commons. Licensed under CC BY-SA 3.0.

In a process known as lysogeny, a phage integrates its genome into a bacterial chromosome. The phage, now called a prophage, is then inherited by subsequent generations during cell replication. These integrations are often incredibly stable, to the extent that prophages are considered to be permanent features of many bacterial genomes. But bacteria have mechanisms to fight off viruses, so why wouldn’t they stop this from happening in the first place?

 

It turns out, prophages come with perks. In addition to genes that are necessary for viral invasion and replication, the phage genome often includes add-ons that provide an evolutionary advantage to the host. These may include genes that confer resistance to antibiotics, contribute to bacterial pathogenicity, or even help kill other microbes. It is beneficial to keep the phage around because it helps the bacteria to be more competitive in its environment. In other words, endogenous viruses drive the evolution of microbes.

Bacteria are useful models for examining rapid-scale evolution. In the span of a few days, or even hours, the prophage-carrying cells may begin to dominate the population. But could lysogenic viruses have possibly impacted the evolution of complex organisms as well?

A Macro Perspective

Mammals are unique within the animal kingdom in terms of prenatal development. The majority of this group develop a placenta and give birth to large and fully developed babies, a tactic which decreases the total number of offspring but increases the odds that they will survive to reproductive age. The placenta itself is a fascinating organ, derived partly from maternal uterine tissue and partly from the fetal blastocyst. The earliest stages of mammalian development require an astounding degree of genetic coordination.

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These eight cells make up an early human embryo. Image credit: Public Domain, via Wikimedia Commons.

Strikingly, researchers have found that many of the viral regions of our DNA are highly expressed in both the placenta and the embryo in these early stages. Some hypothesize that viral genes could help the newly formed embryo evade the mother’s immune system. Other studies have found that viral genes may help embryonic stem cells to differentiate into the various tissues that make up a functional human.

Studies to determine the consequences of our viral ancestry are still in their early days. However, initial findings suggest that we exploit ancient viral genes to assist with the extremely complex genetic program required for early embryonic development. The fact that certain viral regions of primate genomes have remained largely unchanged over the millennia suggests that they likely serve an important function.

Designs by Virus

Viruses are thought to have broadly shaped genomes throughout all domains of life, and it’s not difficult to see why. Their life cycle is dependent on delivering foreign genetic material into an organism. Ultimately, evolution would be impossible without novel DNA. So while you’re still allowed to curse the virus that made you miss your last exam, know that your very existence may have depended on our ancestors’ ancient flu.

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Influenza virus bound to a respiratory tract cell. Image Credit: Public Domain, via Center for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD).

Jennifer Kuraz

Jennifer Kurasz is a graduate student in the Department of Microbiology at UGA, where she studies the regulation of RNA repair mechanisms in Salmonella. When not in the lab, she prefers to be mediocre at many hobbies rather than settle on one. She greatly enjoys her women’s weightlifting group, cooking, painting, meditation, craft beer, and any activity that gets her outdoors. She can be contacted at jennifer.kurasz25@uga.edu. More from Jennifer Kurasz.