Ten millennia of hepatitis B virus evolution

Nature communications, 2024

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2-B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries. Hepatitis B virus (HBV) belongs to an ancient family of hepatotropic DNA viruses, with origins dating back millions of years 1 , and still poses a major health burden to humans nowadays 2,3. HBV infection can lead to both acute and chronic diseases, elevating the risk of cirrhosis and liver cancer-associated mortality 4-6. HBV strains have been classified into 10 genotypes (A-J) based on nucleotide differences in their complete genome sequences 7-9. The distribution of HBV genotypes exhibits similarities among countries within the same geographic region but exhibits marked variations across different parts of the world 10. While genotypes A and D are globally distributed, genotypes E-J are confined to specific regions and contribute to a smaller proportion of infections worldwide 10-13. Genotypes B and C are highly

Nature, 2024

Western Eurasia witnessed several large-scale human migrations during the Holocene [4] . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periodsfrom across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

bioRxiv (Cold Spring Harbor Laboratory), 2022

Several major migrations and population turnover events during the later Stone Age (after c. 11,000 cal. BP) are believed to have shaped the contemporary population genetic diversity in Eurasia. While the genetic impacts of these migrations have been investigated on regional scales, a detailed understanding of their spatiotemporal dynamics both within and between major geographic regions across Northern Eurasia remains largely elusive. Here, we present the largest shotgun-sequenced genomic dataset from the Stone Age to date, representing 317 primarily Mesolithic and Neolithic individuals from across Eurasia, with associated radiocarbon dates, stable isotope data, and pollen records. Using recent advances, we imputed >1,600 ancient genomes to obtain accurate diploid genotypes, enabling previously unachievable fine-grained population structure inferences. We show that 1) Eurasian Mesolitic hunter-gatherers were more genetically diverse than previously known, and deeply divergent between the west and the east; 2) Hitherto genetically undescribed huntergatherers from the Middle Don region contributed significant ancestry to the later Yamnaya steppe pastoralists; 3) The genetic impact of the transition from Mesolithic hunter-gatherers to Neolithic farmers was highly distinct, east and west of a "Great Divide" boundary zone extending from the Black Sea to the Baltic, with large-scale shifts in genetic ancestry to the west. This include an almost complete replacement of hunter-gatherers in Denmark, but no substantial shifts during the same period further to the east; 4) Within-group relatedness changes substantially during the Neolithic transition in the west, where clusters of Neolithic farmer-associated individuals show overall reduced relatedness, while genetic relatedness remains high until ~4,000 BP in the east, consistent with a much longer persistence of smaller localised hunter-gatherer groups; 5) A fastpaced second major genetic transformation beginning around 5,000 BP, with Steppe-related ancestry reaching most parts of Europe within a 1,000 years span. Local Neolithic farmers admixed with incoming pastoralists in most parts of Europe, whereas Scandinavia experienced another nearcomplete population replacement, with similar dramatic turnover-patterns also evident in western Siberia; 6) Extensive regional differences in the ancestry components related to these early events remain visible to this day, even within countries (research conducted using the UK Biobank resource). Neolithic farmer ancestry is highest in southern and eastern England while Steppe-related ancestry is highest in the Celtic populations of Scotland, Wales, and Cornwall. Overall, our findings show that although the Stone-Age migrations have been important in shaping contemporary genetic diversity in Eurasia, their dynamics and impact were geographically highly heterogeneous.

Nature, 2018

Nature Research wishes to improve the reproducibility of the work that we publish. This form provides structure for consistency and transparency in reporting. For further information on Nature Research policies, see Authors & Referees and the Editorial Policy Checklist.

Nature, 2024

Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers.

International Open Workshop "Socio-Environmental Dynamics over the Last 15,000 Years: The Creation of Landscapes VI". Conference Reader, 2019

Nature

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdal...

2021

Recent studies showed that Neolithic populations in southwest Asia included distinct gene pools in the Levant, in Central Anatolia, and in the Zagros. Further, genomic comparisons suggested that all three populations adopted sedentism and farming without major admixture or replacement from other regions. Meanwhile, the population genetic characteristics of the geographic midpoint of these regions, namely upper Mesopotamia, has not been investigated so far. Here in this study, we present the first genomic data of individuals excavated from the PPNB phase of Çayönü. Çayönü, near the upper stretches of river Tigris, is one of the early settlements discovered in southeast Anatolia at the upper-most edge of Fertile Crescent. Material culture data indicate that the Çayönü population interacted intensely with nearby regions - Anatolia, Levant, and Zagros. Despite poor DNA preservation due to harsh environmental conditions, after screening the remains of 33 individuals we managed to obtain ...

Nature, 2018

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.

2021

How the advent of agriculture and social complexity changed human inbreeding patterns is unclear. Ethnographic work suggests low levels of consanguinity in modern-day foragers compared to farmer communities. Meanwhile, the larger population sizes of farmer societies may have lowered the frequency of panmictic (i.e. drift-driven) inbreeding in these groups. Hence, the net impact of food production on autozygosity levels remains unknown. Here we show that runs of homozygosity (ROH) >1 Mb can be reliably estimated in genomes with ≥3x mean coverage per SNP. We thus calculate the ROH-based inbreeding coefficient estimate, or FROH, in 411 published ancient Eurasian genomes from the last 15,000 years. We find that FROH has significantly decreased over time, in both West and Central Eurasia. The most dramatic reduction appears associated with the Neolithic Transition. Our results hence suggest that population growth caused by food production, along withincreased rates of human mobility, ...