hepatitis B

New research analyses the evolution of the last ten thousand years of the hepatitis B virus

The University of Valencia participates in a research on the evolution of the last ten thousand years of the hepatitis B virus

A study published in the journal Science traces the evolution of the hepatitis B virus from prehistory to the present, revealing dissemination routes and changes in viral diversity. Domingo Carlos Salazar García, researcher from the Prehistory, Archeology and Ancient History Department of the University of Valencia, has participated in this study led by the Max Planck Institute for the Science of Human History (Germany). The research uncovers the evolution of the hepatitis B virus since the Early Holocene by analyzing the largest dataset of ancient viral genomes produced to date.

hepatitis B
Domingo Carlos Salazar García, researcher from the Prehistory, Archeology and Ancient History Department of the University of Valencia

“This research puts upfront a reality many times ignored but obvious, that viruses have been linked to humans since prehistoric times”, highlighted Salazar, graduated in Medicine and in History, researcher of excellence of the Valencian Community at the University of Valencia. “If SARS-COV-2 has been able to put human societies in check worldwide during the twenty-first century, we can only begin to imagine how viral diseases influenced life in prehistoric times”, he explains. “Historians and archaeologists must start considering more the influence of viruses and other agents that until now have been invisible on the archaeological record when reconstructing past lifestyles”, he says.

The hepatitis B virus (HBV) is a major health problem worldwide, causing close to one million deaths each year. Recent ancient DNA studies have shown that HBV has been infecting humans for millennia, but its past diversity and dispersal routes remain largely unknown. A new study conducted by a large team of researchers from all around the world provides major insights into the evolutionary history of HBV by examining the virus’ genomes from 137 ancient Eurasians and Native Americans dated between ~10,500 and ~400 years ago. Their results highlight dissemination routes and shifts in viral diversity that mirror well-known human migrations and demographic events, as well as unexpected patterns and connections to the present.

Present-day HBV strains are classified into nine genotypes, two of which are found predominantly in populations of Native American ancestry. The study provides strong evidence that these strains descend from an HBV lineage that diverged around the end of the Pleistocene and was carried by some of the first inhabitants of the Americas.

“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”, says Denise Kühnert, leader of the research group.


HBV in prehistoric Europe

The study also shows that the virus was present in large parts of Europe as early as 10,000 years ago, before the spread of agriculture to the continent. “Many human pathogens are thought to have emerged after the introduction of agriculture, but HBV was clearly already affecting prehistoric hunter-gatherer populations”, says Johannes Krause, director of the Department of Archaeogenetics at the Max Planck Institute for Evolutionary Anthropology and co-supervisor of the study.

After the Neolithic transition in Europe, the HBV strains carried by hunter-gatherers were replaced by new strains that were likely spread by the continent’s first farmers, mirroring the large genetic influx associated with the expansion of farming groups across the region. These new viral lineages continued to prevail throughout western Eurasia for around 4,000 years. The dominance of these strains lasted through the expansion of Western Steppe Herders around 5,000 years ago, which dramatically altered the genetic profile of Europeans but remarkably was not associated with the spread of new HBV variants.


The collapse and re-emergence of pre-historic HBV

One of the most surprising findings of the study is a sudden decline of HBV diversity in western Eurasia during the second half of the 2nd millennium BCE, a time of major cultural shifts, including the collapse of large Bronze Age state societies in the eastern Mediterranean region.

“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”, says Arthur Kocher, lead author and researcher in the group.

All ancient HBV strains recovered in western Eurasia after this period belonged to new viral lineages that still prevail in the region today. However, it appears that one variant related to the previous prehistoric diversity of the region has persisted to the present. This prehistoric variant has evolved into a rare genotype that seems to have emerged recently during the HIV pandemic, for reasons that remain to be understood.


Article: Kocher et al. “Ten millennia of hepatitis B virus evolution”, Science, 2021. DOI: https://www.science.org/doi/10.1126/science.abi5658

Press release from the University of Valencia and Asociación RUVID.

Details of first historically recorded plague pandemic revealed by ancient genomes

Details of first historically recorded plague pandemic revealed by ancient genomes

Analysis of 8 new plague genomes from the first plague pandemic reveals previously unknown levels of plague diversity, and provides the first genetic evidence of the Justinianic Plague in the British Isles

Justinianic Plague Yersinia pestis
Map and phylogenetic tree showing the newly published (yellow) and previously published (turquoise) genomes. Shaded areas and dots represent historically recorded outbreaks of the First Pandemic. Credit: Marcel Keller

An international team of researchers has analyzed human remains from 21 archaeological sites to learn more about the impact and evolution of the plague-causing bacterium Yersinia pestis during the first plague pandemic (541-750 AD). In a study published in PNAS, the researchers reconstructed 8 plague genomes from Britain, Germany, France and Spain and uncovered a previously unknown level of diversity in Y. pestis strains. Additionally, they found the first direct genetic evidence of the Justinianic Plague in the British Isles.

The Justinianic Plague began in 541 in the Eastern Roman Empire, ruled at the time by the Emperor Justinian I, and recurrent outbreaks ravaged Europe and the Mediterranean basin for approximately 200 years. Contemporaneous records describe the extent of the pandemic, estimated to have wiped out up to 25% of the population of the Roman world at the time. Recent genetic studies revealed that the bacterium Yersinia pestis was the cause of the disease, but how it had spread and how the strains that appeared over the course of the pandemic were related to each other was previously unknown.

In the current study, an international team of researchers led by the Max Planck Institute for the Science of Human History analyzed human remains from 21 sites with multiple burials in Austria, Britain, Germany, France and Spain. They were able to reconstruct 8 new Y. pestis genomes, allowing them to compare these strains to previously published ancient and modern genomes. Additionally, the team found the earliest genetic evidence of plague in Britain, from the Anglo-Saxon site of Edix Hill. By using a combination of archaeological dating and the position of this strain of Y. pestis in its evolutionary tree, the researchers concluded that the genome is likely related to an ambiguously described pestilence in the British Isles in 544 AD.

High diversity of Y. pestis strains during the First Pandemic

The researchers found that there was a previously unknown diversity of strains of Y. pestis circulating in Europe between the 6th and 8th centuries AD. The 8 new genomes came from Britain, France, Germany and Spain. "The retrieval of genomes that span a wide geographic and temporal scope gives us the opportunity to assess Y. pestis' microdiversity present in Europe during the First Pandemic," explains co-first author Marcel Keller, PhD student at the Max Planck Institute for the Science of Human History, now working at the University of Tartu. The newly discovered genomes revealed that there were multiple, closely related strains of Y. pestis circulating during the 200 years of the First Pandemic, some possibly at the same times and in the same regions.

Despite the greatly increased number of genomes now available, the researchers were not able to clarify the onset of the Justinianic Plague. "The lineage likely emerged in Central Asia several hundred years before the First Pandemic, but we interpret the current data as insufficient to resolve the origin of the Justinianic Plague as a human epidemic, before it was first reported in Egypt in 541 AD. However, the fact that all genomes belong to the same lineage is indicative of a persistence of plague in Europe or the Mediterranean basin over this time period, instead of multiple reintroductions."

Sampling of a tooth from a suspected plague burial. Credit: Evelyn Guevara

Possible evidence of convergent evolution in strains from two independent historical pandemics

Another interesting finding of the study was that plague genomes appearing towards the end of the First Pandemic showed a big deletion in their genetic code that included two virulence factors. Plague genomes from the late stages of the Second Pandemic some 800-1000 years later show a similar deletion covering the same region of the genomes. "This is a possible example of convergent evolution, meaning that these Y. pestis strains independently evolved similar characteristics. Such changes may reflect an adaptation to a distinct ecological niche in Western Eurasia where the plague was circulating during both pandemics," explains co-first author Maria Spyrou of the Max Planck Institute for the Science of Human History.

The current study offers new insights into the first historically documented plague pandemic, and provides additional clues alongside historical, archaeological, and palaeoepidemiological evidence, helping to answer outstanding questions. "This study shows the potential of palaeogenomic research for understanding historical and modern pandemics by comparing genomes across millennia," explains senior author Johannes Krause of the Max Planck Institute for the Science of Human History. "With more extensive sampling of possible plague burials, we hope to contribute to the understanding of Y. pestis' microevolution and its impact on humans during the course of past and present pandemics."

Lunel-Viel (Languedoc-Southern France). Victim of the plague thrown into a demolition trench of a Gallo-Roman house; end of the 6th-early 7th century. Credit: 1990; CNRS - Claude Raynaud

Press release from the Max Planck Institute for the Science of Human History / Max-Planck-Instituts für Menschheitsgeschichte

Inner Eurasia

Details of the history of inner Eurasia revealed by new study

Details of the history of inner Eurasia revealed by new study

Researchers combining genetics, archaeology, history and linguistics have gained new insights into the history of inner Eurasia, once a cultural and genetic crossroads connecting Europe and Asia

Inner Eurasia
Children from one of the Tajikistan communities included in the study. Credit: Elena Balanovska

An international team of researchers has combined archaeological, historical and linguistic data with genetic information from over 700 newly analyzed individuals to construct a more detailed picture of the history of inner Eurasia than ever before available. In a study published in Nature Ecology & Evolution, they found that the indigenous populations of inner Eurasia are very diverse in their genes, culture and languages, but divide into three groups that stretch across the area in east-west geographic bands.

Inner Eurasia, including areas of modern-day Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine and Uzbekistan, was once the cross-roads connecting Asia and Europe, and a major intersection for the exchange of culture, trade goods and genes in prehistory and historical periods, including the era of the famous Silk Road.

This vast area can also be divided into several distinct ecological regions that stretch in largely east-west bands across Inner Eurasia, consisting of the deserts at the southern edge of the region, the steppe in the central part, taiga forests further north, and tundra towards the Arctic region. The subsistence strategies used by indigenous groups in these regions largely correlate with the ecological zones, for example reindeer herding and hunting in the tundra region and nomadic pastoralism on the steppe.

Despite the long and important history of inner Eurasia, details about past migrations and interactions between groups are not always clear, especially in prehistory. "Inner Eurasia is a perfect place to investigate the relationship between environmental conditions and the pattern of human migration and mixture, as well as changes driven by cultural innovations such as the introduction of dairy pastoralism into the steppe," states Choongwon Jeong of the Max Planck Institute for the Science of Human History, co-first and senior author of the paper. In order to clarify our understanding of some of the nuances of the history of the region, an international team of researchers undertook an ambitious project to use modern and ancient DNA from a broad geographic range and time period, in concert with archaeological, linguistic and historical information, to clarify the relationships between the different populations. "A few ethnic groups were studied previously," comments Oleg Balanovsky from the Vavilov Institute of General Genetics in Moscow, also co-first author, "but we conducted more than a hundred field trips to study this vast region systematically, and reached communities speaking almost all of the Inner Eurasian languages".

Three distinct east-west groupings

For this study, the researchers analyzed DNA from 763 individuals from across the region as well as reanalyzed the genome-wide data from two ancient individuals from the Botai culture, and compared those results with previously published data from modern and ancient individuals. They found three distinct genetic groupings, which geographically are arranged in east-west bands stretching across the region and correlating generally to ecological zones, where populations within each band share a distinct combination of ancestries in varying proportions.

The northernmost grouping, which they term "forest-tundra", includes Russians, all Uralic language-speakers, which includes Hungarian, Finnish and Estonian, and Yeniseian-language speakers, of which only one remains today and is spoken in central Siberia. The middle grouping, which they term "steppe-forest", includes Turkic- and Mongolic-speaking populations from the Volga and the region around the Altai and Sayan mountains, near to where Russia, China, Mongolia and Kazakhstan meet. The southernmost grouping, "southern-steppe", includes the rest of Turkic- and Mongolic-speaking populations living further south, such as Kazakhs, Kyrgyzs and Uzbeks, as well as Indo-European-speaking Tajiks.

Previously unknown genetic connections revealed

Because the study includes data from a broad time period, it is able to show shifts in ancestry in the past that reveal previously unknown interactions. For example, the researchers found that the southern-steppe populations had a larger genetic component from West and South Asia than the other two groupings. This component is also widespread in the ancient populations of the region since the second half of the first millennium BC, but not found in Central Kazakhstan in earlier periods. This hints at a population movement from the southern-steppe region to the steppe-forest region that was previously unknown.

"Inner Eurasia has functioned as a conduit for human migration and cultural transfer since the first appearance of modern humans in this region. As a result, we observe deep sharing of genes between Western and Eastern Eurasian populations in multiple layers," explains Jeong. "The opportunity to find direct evidence for the hidden old layers of admixture, which is often difficult to appreciate from present-day populations, is very exciting."

"We found not only corridors, but also barriers for migrations," adds Balanovsky. "Some of them separate the historical groups of populations, while others, like the distinct barrier following the Great Caucasus mountain ridge, were obviously shaped by the geographic landscape."

Geographic locations of the Eneolithic Botai, groups including newly sampled individuals, and nearby groups with published data. The map is overlayed with ecoregional information, divided into 14 biomes downloaded from https://ecoregions2017.appspot.com/ (credited to Ecoregions 2017 © Resolve). Credit: Jeong & Balanovsky et. al. 2019. The genetic history of admixture across inner Eurasia. Nature Ecology & Evolution, http://dx.doi.org/10.1038/s41559-019-0878-2.

Two ancient individuals resequenced in this study originated from the Botai culture in Kazakhstan where the horse was initially domesticated. Analysis of the Y-chromosome (inherited along the paternal genealogical lines) revealed a genetic lineage which is typical in the Kazakh steppe up to the present day. But analysis of the autosomes, which both parents contribute to their children, show no trace of Botai ancestry left in present-day people, likely due to repeated migrations into the region both from the west and the east since the Bronze Age.

The researchers emphasize that their model of three groupings does not perfectly explain all known populations and that there are examples of both outliers and intermediate groups. "It is important to organize a future study for further sampling of sparsely populated regions between the clines, for example, Central Kazakhstan or East Siberia," states Johannes Krause, also of the Max Planck Institute for the Science of Human History, and senior author of the paper.

Researchers from the study conducting field work along the Amur River. Credit: Yuri Bogunov

Press release from the Max Planck Institute for the Science of Human History / Max-Planck-Institut für Menschheitsgeschichte