The liver-destroying hepatitis B virus (HBV) kills nearly a million people each year. Now, a pair of new genetic studies suggests the pathogen has been with us at least since the dawn of civilization.
Until now, the oldest evidence for HBV was a strain discovered in a 16th century Italian mummy. In the new work, a team led by geneticist Eske Willerslev of the University of Cambridge in the United Kingdom sequenced the whole genomes of 304 people found at archaeological sites throughout Eurasia, most dating to the Bronze and Iron ages (approximately 3500 B.C.E. through 500 B.C.E.). They quickly recognized the genetic signature of HBV in 12 individuals. The oldest sample, from a man, was about 4500 years old and found in an ancient grave in Osterhofen, Germany.
The team then compared the DNA sequences of these ancient viruses with modern versions of HBV and used advanced mathematical modeling techniques to estimate how long it would take for these variations to arise given their prevalence in populations through time. The data revealed that the virus likely originated roughly between 13,600 B.C.E. and 9600 B.C.E., they report today in Nature.
Another study led by geneticist Johannes Krause at the Max Planck Institute for the Science of Human History in Jena, Germany, found traces of HBV in the dental pulp of three skeletons from Germany dating from 3200 B.C.E. to 5000 B.C.E. Considering the results of both studies, “[HBV] seems to have been pretty common in the past,” says Krause, whose team reported its work earlier this week in a paper published to the bioRxiv preprint server. That’s not necessarily a surprise, he says, but it points the way for future researchers to investigate other ancient diseases.
One popular hypothesis, based on the fact that chimpanzees and gorillas have strains of HBV extremely similar to humans, has suggested the virus may have arisen in Africa, then jumped into humans through blood-to-blood contact during hunting or cutting their meat. From there, the virus could have proliferated into different strains as humans filtered out into Eurasia about 80,000 to 120,000 years ago.
Willerslev’s team’s findings suggest an intriguing alternate possibility: that HBV may have arisen much more recently in humans living in Eurasia or even North America, then was transmitted to both humans and nonhuman primates in Africa, although the mechanism of such a transmission is murky. This timeline dovetails with the beginnings of human civilization, when larger populations and trade routes would have helped the disease spread and transform into novel strains.
Krause, however, is skeptical about estimates of when the virus arose. HBV recombines genetic material from its host, so typical molecular dating techniques based on rates of genetic mutation don’t work, he says.
Hendrik Poinar, an evolutionary geneticist at McMaster University in Hamilton, Canada, who wasn’t involved in the research, agrees that these limitations make it difficult to speculate on the chronological origins of the virus given current data. “Saying anything about the timing of HBV’s origins is dicey at this point.”
But regardless of HBV’s age, “These papers show really beautifully that you can find samples of pathogens in DNA that is thousands of years old,” he says. “This virus’s interaction with humans is a dynamic that has been playing out over millennia.”