Mammals Carry a Graveyard of Viruses in Our DNA, And It Could Have a Crucial Purpose

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HEALTH
TESSA KOUMOUNDOUROS
11 SEPTEMBER 2021


Huge swaths of our DNA library are made up of non-coding genes that were long regarded as "junk DNA". Recent findings, however, have shown these bits of DNA actually have many purposes in mammals.

Some help form the structure in our DNA molecules so they can be packaged neatly within our cell nuclei while others are involved in gene regulation. Now, researchers from the University of New South Wales in Australia have discovered another potential purpose for these non-coding instructions, within the genomes of marsupials.

Some of the gene sequences once considered "junk" are actually fragments of viruses left buried in our DNA from an infection in a long-forgotten ancestor.

Whenever a virus infects you, there's a chance it will leave behind a piece of itself within your DNA, and if this happens in an egg or sperm cell, it will then be passed on through the generations. These are known as endogenous viral elements (EVEs).

In humans, fragments of viral DNA make up around 8 percent of our genome. They can provide a record of viral infections through our evolutionary history, like genetic memory.

"These viral fragments have been retained for a reason," said paleovirologist Emma Harding. "Over millions of years of evolution, we would expect all DNA to change, however, these fossils are preserved and kept intact."

To try to work out why, Harding and colleagues searched for EVEs in the genomes of 13 species of marsupials, including the tammar wallaby (Macropus eugeni), Tasmanian devil (Sarcophilus harrisii), and fat-tailed dunnarts (Sminthopsis crassicaudata).

They found EVEs from three viral groups – Bornaviridae, Filoviridae, and Parvoviridae – in all of the animals sampled.

"One of the EVEs I found was from the Bornaviridae family of viruses, which first entered the animals' DNA during the time of the dinosaurs when the South American and Australian land masses were still joined together," Harding said. Bornaviridae is present in the opossums of America as well as Australia's marsupials.

The Bornaviridae EVEs were particularly prevalent and more closely related to similar viral fossils found in birds and reptiles rather than those seen in placental mammals like us.

"Bornaviridae viruses were previously thought to have evolved 100 million years ago," Harding explained. "But the one I found in almost every marsupial DNA we looked at puts it at 160 million years old."

Surprisingly, some of these ancient viral fragments were still being transcribed into RNA. Often in cells, RNA transcriptions act as protein templates. But in this case they weren't being translated, effectively making them non-coding RNA.

That doesn't make them useless. Non-coding RNA is used in a number of cell functions, including the regulation of RNA transcription among other genes.

A tammar wallaby, one of the study species. (Hossein Anv/Unsplash)

Significantly, it is also known that this type of RNA is used for many cell functions, including regulating the creation of RNA, and it is also known to contribute to immune defense against viruses in plants and invertebrates. Bats have a particularly large cache of these fossil viral fragments too, and they're well known for their unfortunate ability to survive while carrying deadly viruses that do most other mammals in.

Looking at koalas in more detail, the researchers discovered some of the EVEs were indeed being transcribed into small RNA molecules known to be antiviral in invertebrates.


"This suggests the tantalizing possibility of this RNA defense system, previously thought to be abandoned in mammals in favor of the interferon system, still being active and protecting marsupial cells," Harding and colleagues wrote in Microbiology Australia.

As marsupials undergo most of their developmental time within their mother's pouch, some are born before they've even developed bones let alone fully functioning immune systems. So, this kind of antiviral defense could be critical to pouch young, the team suspects.

"This could be a mechanism similar to vaccination but is inherited through generations. By keeping a viral fossil, the cell is immunized against future infection," said Harding.

"If we can show it occurring in marsupials, it may also be occurring in other animals, including humans."

This researcher was published in Virus Evolution.