Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations.

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that is most prevalent in Northern Europe. Although it is known that inherited risk for MS is located within or in close proximity to immune-related genes, it is unknown when, where and how this genetic risk originated1. Here, by using a large ancient genome dataset from the Mesolithic period to the Bronze Age2, along with new Medieval and post-Medieval genomes, we show that the genetic risk for MS rose among pastoralists from the Pontic steppe and was brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the steppe population and later in Europe, probably driven by pathogenic challenges coinciding with changes in diet, lifestyle and population density. This study highlights the critical importance of the Neolithic period and Bronze Age as determinants of modern immune responses and their subsequent effect on the risk of developing MS in a changing environment.

The selection landscape and genetic legacy of ancient Eurasians.

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer's disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans.

Genomic Steppe ancestry in skeletons from the Neolithic Single Grave Culture in Denmark.

The Gjerrild burial provides the largest and best-preserved assemblage of human skeletal material presently known from the Single Grave Culture (SGC) in Denmark. For generations it has been debated among archaeologists if the appearance of this archaeological complex represents a continuation of the previous Neolithic communities, or was facilitated by incoming migrants. We sampled and analysed five skeletons from the Gjerrild cist, buried over a period of c. 300 years, 2600/2500-2200 cal BCE. Despite poor DNA preservation, we managed to sequence the genome (>1X) of one individual and the partial genomes (0.007X and 0.02X) of another two individuals. Our genetic data document a female (Gjerrild 1) and two males (Gjerrild 5 + 8), harbouring typical Neolithic K2a and HV0 mtDNA haplogroups, but also a rare basal variant of the R1b1 Y-chromosomal haplogroup. Genome-wide analyses demonstrate that these people had a significant Yamnaya-derived (i.e. steppe) ancestry component and a close genetic resemblance to the Corded Ware (and related) groups that were present in large parts of Northern and Central Europe at the time. Assuming that the Gjerrild skeletons are genetically representative of the population of the SGC in broader terms, the transition from the local Neolithic Funnel Beaker Culture (TRB) to SGC is not characterized by demographic continuity. Rather, the emergence of SGC in Denmark was part of the Late Neolithic and Early Bronze Age population expansion that swept across the European continent in the 3rd millennium BCE, resulting in various degrees of genetic replacement and admixture processes with previous Neolithic populations.

The spatiotemporal spread of human migrations during the European Holocene.

The European continent was subject to two major migrations of peoples during the Holocene: the northwestward movement of Anatolian farmer populations during the Neolithic and the westward movement of Yamnaya steppe peoples during the Bronze Age. These movements changed the genetic composition of the continent's inhabitants. The Holocene was also characterized by major changes in vegetation composition, which altered the environment occupied by the original hunter-gatherer populations. We aim to test to what extent vegetation change through time is associated with changes in population composition as a consequence of these migrations, or with changes in climate. Using ancient DNA in combination with geostatistical techniques, we produce detailed maps of ancient population movements, which allow us to visualize how these migrations unfolded through time and space. We find that the spread of Neolithic farmer ancestry had a two-pronged wavefront, in agreement with similar findings on the cultural spread of farming from radiocarbon-dated archaeological sites. This movement, however, did not have a strong association with changes in the vegetational landscape. In contrast, the Yamnaya migration speed was at least twice as fast and coincided with a reduction in the amount of broad-leaf forest and an increase in the amount of pasture and natural grasslands in the continent. We demonstrate the utility of integrating ancient genomes with archaeometric datasets in a spatiotemporal statistical framework, which we foresee will enable future studies of ancient populations' movements, and their putative effects on local fauna and flora.

The population history of northeastern Siberia since the Pleistocene.

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.

Unraveling ancestry, kinship, and violence in a Late Neolithic mass grave.

The third millennium BCE was a period of major cultural and demographic changes in Europe that signaled the beginning of the Bronze Age. People from the Pontic steppe expanded westward, leading to the formation of the Corded Ware complex and transforming the genetic landscape of Europe. At the time, the Globular Amphora culture (3300-2700 BCE) existed over large parts of Central and Eastern Europe, but little is known about their interaction with neighboring Corded Ware groups and steppe societies. Here we present a detailed study of a Late Neolithic mass grave from southern Poland belonging to the Globular Amphora culture and containing the remains of 15 men, women, and children, all killed by blows to the head. We sequenced their genomes to between 1.1- and 3.9-fold coverage and performed kinship analyses that demonstrate that the individuals belonged to a large extended family. The bodies had been carefully laid out according to kin relationships by someone who evidently knew the deceased. From a population genetic viewpoint, the people from Koszyce are clearly distinct from neighboring Corded Ware groups because of their lack of steppe-related ancestry. Although the reason for the massacre is unknown, it is possible that it was connected with the expansion of Corded Ware groups, which may have resulted in competition for resources and violent conflict. Together with the archaeological evidence, these analyses provide an unprecedented level of insight into the kinship structure and social behavior of a Late Neolithic community.

Emergence and Spread of Basal Lineages of Yersinia pestis during the Neolithic Decline.

Between 5,000 and 6,000 years ago, many Neolithic societies declined throughout western Eurasia due to a combination of factors that are still largely debated. Here, we report the discovery and genome reconstruction of Yersinia pestis, the etiological agent of plague, in Neolithic farmers in Sweden, pre-dating and basal to all modern and ancient known strains of this pathogen. We investigated the history of this strain by combining phylogenetic and molecular clock analyses of the bacterial genome, detailed archaeological information, and genomic analyses from infected individuals and hundreds of ancient human samples across Eurasia. These analyses revealed that multiple and independent lineages of Y. pestis branched and expanded across Eurasia during the Neolithic decline, spreading most likely through early trade networks rather than massive human migrations. Our results are consistent with the existence of a prehistoric plague pandemic that likely contributed to the decay of Neolithic populations in Europe.

The first horse herders and the impact of early Bronze Age steppe expansions into Asia.

The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (~3000 BCE) are believed to have brought with them Indo-European languages and possibly horse husbandry. We analyzed 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after, but not at the time of, Yamnaya culture. We find no evidence of steppe ancestry in Bronze Age Anatolia from when Indo-European languages are attested there. Thus, in contrast to Europe, Early Bronze Age Yamnaya-related migrations had limited direct genetic impact in Asia.

Ancient hepatitis B viruses from the Bronze Age to the Medieval period.

Hepatitis B virus (HBV) is a major cause of human hepatitis. There is considerable uncertainty about the timescale of its evolution and its association with humans. Here we present 12 full or partial ancient HBV genomes that are between approximately 0.8 and 4.5 thousand years old. The ancient sequences group either within or in a sister relationship with extant human or other ape HBV clades. Generally, the genome properties follow those of modern HBV. The root of the HBV tree is projected to between 8.6 and 20.9 thousand years ago, and we estimate a substitution rate of 8.04 × 10-6-1.51 × 10-5 nucleotide substitutions per site per year. In several cases, the geographical locations of the ancient genotypes do not match present-day distributions. Genotypes that today are typical of Africa and Asia, and a subgenotype from India, are shown to have an early Eurasian presence. The geographical and temporal patterns that we observe in ancient and modern HBV genotypes are compatible with well-documented human migrations during the Bronze and Iron Ages1,2. We provide evidence for the creation of HBV genotype A via recombination, and for a long-term association of modern HBV genotypes with humans, including the discovery of a human genotype that is now extinct. These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone.

The Beaker phenomenon and the genomic transformation of northwest Europe.

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

A matter of months: High precision migration chronology of a Bronze Age female.

Establishing the age at which prehistoric individuals move away from their childhood residential location holds crucial information about the socio dynamics and mobility patterns in ancient societies. We present a novel combination of strontium isotope analyses performed on the over 3000 year old "Skrydstrup Woman" from Denmark, for whom we compiled a highly detailed month-scale model of her migration timeline. When combined with physical anthropological analyses this timeline can be related to the chronological age at which the residential location changed. We conducted a series of high-resolution strontium isotope analyses of hard and soft human tissues and combined these with anthropological investigations including CT-scanning and 3D visualizations. The Skrydstrup Woman lived during a pan-European period characterized by technical innovation and great social transformations stimulated by long-distance connections; consequently she represents an important part of both Danish and European prehistory. Our multidisciplinary study involves complementary biochemical, biomolecular and microscopy analyses of her scalp hair. Our results reveal that the Skrydstrup Woman was between 17-18 years old when she died, and that she moved from her place of origin -outside present day Denmark- to the Skrydstrup area in Denmark 47 to 42 months before she died. Hence, she was between 13 to 14 years old when she migrated to and resided in the area around Skrydstrup for the rest of her life. From an archaeological standpoint, this one-time and one-way movement of an elite female during the possible "age of marriageability" might suggest that she migrated with the aim of establishing an alliance between chiefdoms. Consequently, this detailed multidisciplinary investigation provides a novel tool to reconstruct high resolution chronology of individual mobility with the perspective of studying complex patterns of social and economic interaction in prehistory.

Diet and Mobility in the Corded Ware of Central Europe.

Isotopic investigations of two cemetery populations from the Corded Ware Culture in southern Germany reveal new information on the dating of these graves, human diet during this period, and individual mobility. Corded Ware Culture was present across much of temperate Europe ca. 2800-2200 cal. BC and is represented by distinctive artifacts and burial practices. Corded Ware was strongly influenced by the Yamnaya Culture that arose in the steppes of eastern Europe and western Eurasia after 3000 BC, as indicated by recent aDNA research. However, the development of CW on different chronological and spatial scales has to be evaluated. Examination of the CW burials from southern Germany supports an argument for substantial human mobility in this period. Several burials from gravefields and larger samples from two large cemeteries at Lauda-Königshofen "Wöllerspfad" and at Bergheinfeld "Hühnerberg" contributed the human remains for our study of bone and tooth enamel from the Corded Ware Culture. Our results suggest that Corded Ware groups in this region at least were subsisting on a mix of plant and animal foods and were highly mobile, especially the women. We interpret this as indicating a pattern of female exogamy, involving different groups with differing economic strategies.

Early divergent strains of Yersinia pestis in Eurasia 5,000 years ago.

The bacteria Yersinia pestis is the etiological agent of plague and has caused human pandemics with millions of deaths in historic times. How and when it originated remains contentious. Here, we report the oldest direct evidence of Yersinia pestis identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. By sequencing the genomes, we find that these ancient plague strains are basal to all known Yersinia pestis. We find the origins of the Yersinia pestis lineage to be at least two times older than previous estimates. We also identify a temporal sequence of genetic changes that lead to increased virulence and the emergence of the bubonic plague. Our results show that plague infection was endemic in the human populations of Eurasia at least 3,000 years before any historical recordings of pandemics.

Tracing the dynamic life story of a Bronze Age Female.

Ancient human mobility at the individual level is conventionally studied by the diverse application of suitable techniques (e.g. aDNA, radiogenic strontium isotopes, as well as oxygen and lead isotopes) to either hard and/or soft tissues. However, the limited preservation of coexisting hard and soft human tissues hampers the possibilities of investigating high-resolution diachronic mobility periods in the life of a single individual. Here, we present the results of a multidisciplinary study of an exceptionally well preserved circa 3.400-year old Danish Bronze Age female find, known as the Egtved Girl. We applied biomolecular, biochemical and geochemical analyses to reconstruct her mobility and diet. We demonstrate that she originated from a place outside present day Denmark (the island of Bornholm excluded), and that she travelled back and forth over large distances during the final months of her life, while consuming a terrestrial diet with intervals of reduced protein intake. We also provide evidence that all her garments were made of non-locally produced wool. Our study advocates the huge potential of combining biomolecular and biogeochemical provenance tracer analyses to hard and soft tissues of a single ancient individual for the reconstruction of high-resolution human mobility.