Tracing Ancient Viruses

Only recently have genome sequencing and high-volume data analysis offered scientists a chance to look back millions of years at ancient viruses—a form of scientific detective work often referred to as “paleovirology”.

A team led by Professor of Biology Welkin Johnson took one such long look back and revealed the global spread of an ancient group of retroviruses that affected about 28 of 50 modern mammals' ancestors some 15 to 30 million years ago.

One of the most extensive viral evolutionary reconstructions undertaken generated a “family tree” that shows a virus that jumped from one host species to another and crisscrossed all but the polar regions of the globe during its lifetime.

Just as a paleontologist might reconstruct a dinosaur skeleton from a few fossilized bones dug from the Earth, Johnson and his team relied on “viral fossils” – bits of viral genetic sequences that persist today as now harmless codes embedded in the DNA of species that once played host to the viruses.

“You can think of the virus sequences that are in nearly every human genome as molecular viral fossils,” says Johnson, whose research combines traditional, molecular virology with evolutionary genetics, in order to study how viruses adapt to their hosts.

“They hold the secrets to viruses that are now extinct, but in the same way that bones can be used to reconstruct human evolution, these sequences can be used to reconstruct when and where these viruses existed and what species they infected,” says Johnson, who is also chairman of the Biology Department at BC.

Retroviruses are abundant in nature and include human immunodeficiency viruses (HIV-1 and -2) and human T-cell leukemia viruses. The scientists' findings on a specific group of these viruses called ERV-Fc, to be published in the journal eLife, show that they affected a wide range of hosts, including species as diverse as carnivores, rodents, and primates.

The distribution of ERV-Fc among these ancient mammals suggests the viruses spread to every continent except Antarctica and Australia, and that they jumped from one species to another more than 20 times.

The study also places the origins of ERV-Fc at least as far back as the beginning of the Oligocene epoch, a period of dramatic global change marked partly by climatic cooling that led to the Ice Ages. Vast expanses of grasslands emerged around this time, along with large mammals as the world's predominate fauna.

"Viruses have been with us for billions of years, and exist everywhere that life is found. They therefore have a significant impact on the ecology and evolution of all organisms, from bacteria to humans," says Johnson. "Unfortunately, viruses do not leave fossils behind, meaning we know very little about how they originate and evolve."

Using "fossil" remnants, the team sought to uncover the natural history of ERV-Fc. They were especially curious to know where and when these pathogens were found in the ancient world, which species they infected, and how they adapted to their mammalian hosts.

To do this, they first performed an exhaustive search of mammalian genome sequence databases for ERV-Fc loci and then compared the recovered sequences. For each genome with sufficient ERV-Fc sequence, they reconstructed the sequences of proteins representing the virus that colonized the ancestors of that particular species. These sequences were then used to infer the natural history and evolutionary relationships of ERV-Fc-related viruses.

The studies also allowed the team to pinpoint patterns of evolutionary change in the genes of these viruses, reflecting their adaptation to different kinds of mammalian hosts.

Perhaps most interestingly, the researchers found that these viruses often exchanged genes with each other and with other viruses, suggesting that genetic recombination played a significant role in their evolutionary success.

"Mammalian genomes contain hundreds of thousands of ancient viral fossils similar to ERV-Fc," says lead author William E. Diehl, who conducted the study while a post-doctoral researcher in the Johnson lab. Diehl is now at the University of Massachusetts.

"The challenge will now be to use ancient viral sequences for looking back in time, which may prove insightful for predicting the long-term consequences of newly emerging viral infections,” Diehl says. “For example, we could potentially assess the impact of HIV on human health 30 million years from now. The method will allow us to better understand when and why new viruses emerge and how long-term contact with them impacts the evolution of host organisms."

Johnson says the findings may be able to help researchers who are studying contemporary viruses, their jump between species and their emergence in new parts of the world.

“My hope that what we’ve learned here can open up the door for this line of research so the methods and approach the team used becomes something researchers in the lab can use to examine other viruses, including those we live with today,” says Johnson.