Paleovirology paves the way: hepatitis B virus evolution mapped out
Researchers collate hepatitis B virus (HBV) genomic data over the past 10 millennia, illuminating the ancestry of the virus and the origins of the current strains we see today.
The study was led by Arthur Kocher from the Max Planck Institute for the Science of Human History (Jena, Germany), where the majority of the 161 authors in this collaborative study are also affiliated. The researchers used DNA-enrichment techniques to reconstruct large proportions of ancient HBV genomes in skeletal tissues from 137 ancient Eurasians and Native Americans dated between ~10,500 and ~400 years ago. The large-scale paleogenetic analysis investigated the phylogeographic history of HBV to provide insight into the historical diversity of the virus and the ancestral dissemination routes of different strains from 10 millennia ago up to the present day.
HBV infection has been a long-standing threat to human health over many centuries. Even today, the most recent Global Hepatitis Report from the WHO estimates that 257 million people were living with chronic HBV infection in 2015, in turn causing approximately 1 million deaths per year. The partially double-stranded DNA virus has no known environmental or animal reservoir and is transmitted via sexual or perinatal bodily fluids. Therefore, the genetic diversity of HBV is strongly linked to the population dynamics and migration of humans. Despite the prevalence of the virus throughout history, the past diversity and dispersal routes of HBV remained unknown until now.
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Two viral strains are predominantly linked to ancient Native American populations that descend from a HBV lineage from the end of the Pleistocene era. “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,” commented Denise Kühnert (Max Planck Institute for the Science of Human History) co-supervisor of the study.
Contrary to popular belief, the study demonstrates that HBV originated before the advent of human farming and was present as early as 10,000 years ago in Europe. “Many human pathogens are thought to have emerged after the introduction of agriculture, but HBV was clearly already affecting prehistoric hunter-gatherer populations,” explained Johannes Krause (Max Planck Institute for the Science of Human History) co-supervisor of the study. These HBV strains were later replaced during the Neolithic Revolution, spread by the first farmers of the region.
A key finding of the study reveals that there was a sharp decline in HBV genetic diversity in western Eurasia late in the 2nd millennium BCE, around the collapse of large Mediterranean societies in the Bronze Age, a pattern that was not expected to be seen when using genetic and archaeological data alone. “This could point to important changes in epidemiological dynamics over a very large region during this period, but we will need more research to understand what happened,” enlightened Arthur Kocher, lead author.
After investigating the HBV phylogeny, it became clear that the ancient HBV strains found in western Eurasia still exist today. Notably, the variant strain responsible for ancient HBV diversity within the region has evolved from prehistoric variant into a modern rare genotype known as HBV-G. The findings illuminate the potential of paleovirologic studies to help map out the past in order to understand and predict the infectious diseases of the future.
