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Hepatitis B Virus Evolution Untangled Using Ancient DNA

NEW YORK – An international team led by investigators in Germany has retraced hepatitis B virus evolution back to 20,000 years, uncovering evidence of the virus in pre-agricultural populations.

"Our data suggest that all known HBV genotypes descend from a strain that was infecting the ancestors of the First Americans and their closest Eurasian relatives around the time these populations diverged," co-senior and co-corresponding author Denise Kühnert, a researcher affiliated with the Max Planck Institute for the Science of Human History's transmission, infection, diversification, and evolution group and its archaeogenetics department, said in a statement.

Although past studies have linked the spread of HBV to human migrations, leading to distinct clusters of the nine contemporary HBV genotypes in different parts of the world, the authors explained in a paper published in Science on Thursday, details on its origin and early spread remain unresolved.

"Ancient DNA data permits molecular clock calibration, and the time to the most recent common ancestor (tMRCA) of all known HBV has been dated to between [around 21,000 years ago and around 9,000 years ago]," they wrote. "However, the extent of the past diversity of this virus remains generally unknown because only 19 ancient HBV genomes with a limited temporal and geographic distribution have been reconstructed to date."

Using DNA enrichment and sequencing, the researchers assessed 137 ancient HBV isolates associated with Native American or Eurasian remains going back some 400 to 10,500 years. Their phylogenetic analyses suggested HBV lineages share a common ancestor going back between 12,000 and 20,000 years, with HBV infections going back to the early Holocene period in hunter-gather populations in Europe and South America.

"Many human pathogens are thought to have emerged after the introduction of agriculture, but HBV was clearly already affecting prehistoric hunter-gatherer populations," co-senior and co-corresponding author Johannes Krause, director of the Max Planck Institute for Evolutionary Anthropology's archaeogenetics department, said in a statement.

The team noted that a lineage found in ancient Native Americans falls into a clade that diverged from lineages in Eurasia an estimated 12,000 to 16,000 years ago. That lineage appeared to be ancestral to the HBV genotypes that have been documented in individuals from Native American populations today.

In Europe, meanwhile, strains found during the Mesolithic period largely gave way to an HBV lineage suspected of being brought by farming populations. Though that lineage stuck around for thousands of years in western Eurasia, the investigators reported, its prominence eventually waned as well, leaving behind a rare genotype that cropped up again with the spread of HIV.

"[O]ur results reveal patterns that were not expected on the basis of human genetic and archaeological data alone, such as the near complete renewal of western Eurasian HBV diversity around the end of the 2nd millennium BCE," the authors concluded. "These findings highlight that the reconstruction of ancient viral diversity has great potential to contribute to our understanding of human history."