INFECTIOUS INSERTIONS: Today's songbirds are harboring traces of ancient viral strains in their genomes, giving researchers a new understanding of the disease's age and evolutionary history. Image: ISTOCKPHOTO/GLOBAL IP
Viruses can be thought of as hyperspeed shape-shifters, organisms that can adapt quickly to overcome barriers to infection. But recent research has been finding ancient traces of many viruses in animal genomes, DNA insertions that have likely been there for much longer than the viruses were previously thought to have existed at all.
A new study describes evidence of a hepadnavirus (a virus group that includes hepatitis B, which infects humans as well as other mammals and ducks) hiding in the genomes of modern songbirds. By tracing back to these bird species' common ancestors, the researchers behind the new work estimate that this family of viruses has been around for at least 19 million years—and possibly as long as 40 million years—rather than the several thousand years researchers had estimated.
Such a primordial start is difficult to square with how similar these ancient snippets' DNA looks to currently circulating versions of the virus and what we know about viruses' ability to change so rapidly. "It's just something we don't quite grasp in the evolution of viruses," says Cédric Feschotte, an associate professor at the University of Texas Arlington's Department of Biology and co-author of the new study. "I think that's pretty exciting." By complicating the understanding of viral evolution, the new findings also promise to help inform transmission dynamics and the ways in which viruses move among different host species.
The new estimate would slow the average rate of hepadnavirus mutation some 1,000-fold, wrote the researchers of the new the study, published online September 28 in PLoS Biology.
Given the bold new picture of virus evolution that many of this and other recent genomic insertion discoveries imply, however, Feschotte is braced for blowback from the field. But the study's numbers look solid, says Harmit Malik, an evolutionary geneticist at the Fred Hutchinson Cancer Research Center who was not involved in the new research. "There was a fairly high burden of proof" in the study, he says; "I think the authors have done a really good job."
These so-called viral fossils are not mineralized relics but rather bits of genetic code held over in the genome of a modern-day host organism. Until recently, most known viral genomic insertions came from retroviruses, which use host cells' nuclei to replicate—thereby making accidental incorporation into the host's genome more likely than from viruses that replicate outside of the nucleus. The human genome, for example, is thought to owe some 8 percent of its code to endogenous retroviruses. And a July study, published online in PLoS Pathogens, described dozens of examples of viral code in vertebrate genomes—much of which had likely been there for some 40 million years.
As viruses go, hepadnaviruses are a likely candidate to get mixed up with the host's own genetic material. Hepatitis B, a disease that kills some 600,000 people worldwide each year, replicates using RNA, and bits of the virus's genetic material are frequently found inside a host's liver cells.
In order to have become integrated in bird genomes and be passed along for millions of years, however, these hepadnaviruses would have needed to insert genetic material into the sperm or egg cells of their avian hosts. The authors propose that given the viral fossils' time span and diversity, the insertions likely happened on multiple occasions—possibly over the course of millions of years. Feschotte suggests that it is likely having a bit of the virus's code integrated in a bird's genome might have conferred immune protection against similar viruses.
Modern-day viruses are an extremely diverse bunch. Because of the observed quick mutation rates, however, "you could explain away all the diversity as arising from a common ancestor maybe 10,000 years ago," Malik says.
In studying the molecular changes in these viruses, "you would never predict to see something that is 20 million years old that resembles so closely the circulating ones," Feschotte notes. The location of the insertions, however, suggests that these integrations are not modern flukes.