Fragments of ancient viral DNA once dismissed as "junk" may play a role in controlling our genes, according to a new international study.
Using a novel method to trace the evolutionary history of viral DNA, researchers from McGill University and Kyoto University uncovered sequences that had been overlooked in earlier genome annotations.
"If we can clearly map what parts of our genome are specific to humans or primates, and what parts came from viruses, we're one step closer to understanding what makes us human and how our DNA influences health and disease," said Guillaume Bourque, one of the study's lead authors and a professor in McGill's Department of Human Genetics.
About eight per cent of the human genome comes from viruses that infected our ancestors millions of years ago. Once thought to be useless, some of these sequences are now known to help switch genes on and off. The new study, which identifies specific sequences that show regulatory potential, adds to growing evidence that these long-overlooked sequences may play important roles and deserve closer scrutiny.
New method to decode viral DNA
When the human genome was first sequenced 25 years ago, researchers identified the viral DNA but lacked the tools to study it in detail. Using modern technology, the team revisited the genome and found many annotations were outdated or incorrect.
The researchers developed a new method that groups viral sequences by their evolutionary history, rather than by sequence similarity alone. By tracing how the sequences evolved over time, they identified patterns that suggest which ones may help control when genes are turned on or off.
Focusing on a viral DNA family called MER11, the team found that there were not three subtypes, as previously thought, but four. One group, MER11_G4, was especially active in human stem cells and included a unique DNA motif found only in humans and chimpanzees. It was this group that the researchers believe may play a role in switching genes on and off.
"The current annotation of viral DNA in the genome shouldn't be treated as definitive. It's time to revisit and refine it," said Bourque.
A clearer understanding of the genome, he added, could help scientists make sense of genetic mutations linked to cancer and rare diseases.
About the study
"A phylogenetic approach uncovers cryptic endogenous retrovirus subfamilies in the primate lineage" by Xun Chen, Zicong Zhang, Yizhi Yan, Clément Goubert, Guillaume Bourque and Fumitaka Inoue was published July 18 in Science Advances.
The research was supported by the Canadian Institutes of Health Research, the Canada Research Chairs program, the Fonds de recherche du Québec - Santé, and Japan's World Premier International Research Center Initiative.
