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Human co-evolution with the hepatitis B virus

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A transmission electron microscopic (TEM) image of hepatitis B virus (HBV) particles (orange). Credit: CDC/ Dr. Erskine Palmer.

Scientists have searched for DNA from the hepatitis B virus (HBV) in human remains from different eras, found in a Sicilian cave. Grotta dell’Uzzo, on the northern coast of Sicily, has been used through the ages as a burial place and a shelter, and is the site of many discoveries of human remains. HBV has been infecting humans for several millennia, but its evolution is unclear. The recent work was part of a large study by an international team that analysed remains from all over the world to reconstruct how the genetic makeup of this pathogen has changed through the ages.

The researchers isolated viral DNA from bone fragments of a late-Mesolithic hunter-gatherer (from about 8,500 years ago) and of three farmers from the early, medium and late Neolithic (dating between 7,500 and 5,900 years ago). The advent of Neolithic marks the ‘agricultural revolution’, and thus the transition from a hunter-gatherer model to a farmer-herder one. Scientists discovered that the oldest DNA they found in Grotta dell’Uzzo belongs to an ancient virus strain that was widely spread across western Eurasia about 10,000 years ago. The Neolithic samples yielded more recent strains, also found in some Sardinian archaeological sites, that do not descend from the Mesolithic variant1.

“We speculate that hunter-gatherers who most likely migrated from south-eastern Europe brought the oldest strain of the virus to Sicily during the late Mesolithic,” says Marcello Mannino, from Aarhus University in Denmark, a co-author of the study. “Later, farmers probably coming by boat from the Balkan Peninsula or even Greece introduced both agriculture and the Neolithic genotypes of HBV, which replaced the Mesolithic ones”.

What emerged in Grotta dell’Uzzo is in fact a microscale model of what was observed in the larger sample of 137 Eurasian and Native American remains examined in the whole study, explains Francesco Cucca, professor of Medical Genetics at Università di Sassari, which contributed to the study by providing five virus DNA samples from Neolithic and Bronze Age Sardinian remains.

“The DNA leap during the transition from Mesolithic to Neolithic reflects a population substitution,” he says. “Farming is a south-western Asian invention, brought to western Eurasia by migrants that replaced local groups of hunter-gatherers. The population replacement, however, was not complete, so much so that present-day Europeans still have a small part of the Mesolithic and even Paleolithic genomes.”.

Most pathogens, such as SARS-CoV-2, need high population densities to spread, because they cause acute infections and epidemics. But others are able to spread even where population density is low, as was the case when our ancestors lived in small groups of hunter-gatherers. The hepatitis B is one such virus, because it causes almost asymptomatic chronic diseases and long-term damage, and is primarily transmitted from mother to child, or sexually. “Such features allowed HBV to follow our species for millennia,” concludes Cucca. “Now we can use its DNA and ours to trace the evolutionary history of both. In the future, we could do the same with other pathogens.”



  1. 1.

    A. Kocher et al. Science 374, 6564 (2021).

    Article  Google Scholar 

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