Identification of microbial pathogens in Neolithic Scandinavian humans.

With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.

Death of Socrates: a likely case of poison hemlock (Conium maculatum) poisoning.

INTRODUCTION: The death of Socrates in 399 BCE is described in Plato's dialogue, the Phaedo, written an unknown time afterwards from accounts by others. THE EVIDENCE: Socrates' death has almost always been attributed to his drinking an extract of poison hemlock, Conium maculatum, despite apparent discrepancies between the clinical features described in classical translations of the Phaedo and general clinical experience of poisoning with the toxic alkaloids it contains. EVALUATION: Recent acute philological analysis of the original Greek text has resolved many of the discrepancies by showing that the terms used in the classical translations were misinterpretations of the clinical signs described. It is also likely that the unpleasant clinical effects, such as vomiting, abdominal pain, diarrhoea and muscle fasciculation commonly described in modern reports of poison hemlock poisoning, were not mentioned to present the death of Socrates in a way consistent with his philosophical ideals and those of his pupil Plato. CONCLUSIONS: Seen in this way, the death of Socrates can be accepted as a limited case report of Conium maculatum poisoning. Even after reaching that conclusion, intriguing scientific questions remain about the toxicity of the coniine alkaloids and the mechanisms of their effects.

Elevated Southern Hemisphere moisture availability during glacial periods.

Late Pleistocene ice-age climates are routinely characterized as having imposed moisture stress on low- to mid-latitude ecosystems1-5. This idea is largely based on fossil pollen evidence for widespread, low-biomass glacial vegetation, interpreted as indicating climatic dryness6. However, woody plant growth is inhibited under low atmospheric CO2 (refs. 7,8), so understanding glacial environments requires the development of new palaeoclimate indicators that are independent of vegetation9. Here we show that, contrary to expectations, during the past 350 kyr, peaks in southern Australian climatic moisture availability were largely confined to glacial periods, including the Last Glacial Maximum, whereas warm interglacials were relatively dry. By measuring the timing of speleothem growth in the Southern Hemisphere subtropics, which today has a predominantly negative annual moisture balance, we developed a record of climatic moisture availability that is independent of vegetation and extends through multiple glacial-interglacial cycles. Our results demonstrate that a cool-moist response is consistent across the austral subtropics and, in part, may result from reduced evaporation under cool glacial temperatures. Insofar as cold glacial environments in the Southern Hemisphere subtropics have been portrayed as uniformly arid3,10,11, our findings suggest that their characterization as evolutionary or physiological obstacles to movement and expansion of animal, plant and, potentially, human populations10 should be reconsidered.

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.

Redefining the treponemal history through pre-Columbian genomes from Brazil.

The origins of treponemal diseases have long remained unknown, especially considering the sudden onset of the first syphilis epidemic in the late 15th century in Europe and its hypothesized arrival from the Americas with Columbus' expeditions1,2. Recently, ancient DNA evidence has revealed various treponemal infections circulating in early modern Europe and colonial-era Mexico3-6. However, there has been to our knowledge no genomic evidence of treponematosis recovered from either the Americas or the Old World that can be reliably dated to the time before the first trans-Atlantic contacts. Here, we present treponemal genomes from nearly 2,000-year-old human remains from Brazil. We reconstruct four ancient genomes of a prehistoric treponemal pathogen, most closely related to the bejel-causing agent Treponema pallidum endemicum. Contradicting the modern day geographical niche of bejel in the arid regions of the world, the results call into question the previous palaeopathological characterization of treponeme subspecies and showcase their adaptive potential. A high-coverage genome is used to improve molecular clock date estimations, placing the divergence of modern T. pallidum subspecies firmly in pre-Columbian times. Overall, our study demonstrates the opportunities within archaeogenetics to uncover key events in pathogen evolution and emergence, paving the way to new hypotheses on the origin and spread of treponematoses.

100 ancient genomes show repeated population turnovers in Neolithic Denmark.

Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1-4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5-7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.

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.

Population genomics of post-glacial western Eurasia.

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. 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.

Homo sapiens reached the higher latitudes of Europe by 45,000 years ago.

The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian-Ranisian-Jerzmanowician (LRJ), which has been described in northwestern and central Europe5-8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated with an LRJ assemblage at the site Ilsenhöhle in Ranis (Germany). These human remains are among the earliest directly dated Upper Palaeolithic H. sapiens remains in Eurasia. We show that early H. sapiens associated with the LRJ were present in central and northwestern Europe long before the extinction of late Neanderthals in southwestern Europe. Our results strengthen the notion of a patchwork of distinct human populations and technocomplexes present in Europe during this transitional period.

Indigenous Australian genomes show deep structure and rich novel variation.

The Indigenous peoples of Australia have a rich linguistic and cultural history. How this relates to genetic diversity remains largely unknown because of their limited engagement with genomic studies. Here we analyse the genomes of 159 individuals from four remote Indigenous communities, including people who speak a language (Tiwi) not from the most widespread family (Pama-Nyungan). This large collection of Indigenous Australian genomes was made possible by careful community engagement and consultation. We observe exceptionally strong population structure across Australia, driven by divergence times between communities of 26,000-35,000 years ago and long-term low but stable effective population sizes. This demographic history, including early divergence from Papua New Guinean (47,000 years ago) and Eurasian groups1, has generated the highest proportion of previously undescribed genetic variation seen outside Africa and the most extended homozygosity compared with global samples. A substantial proportion of this variation is not observed in global reference panels or clinical datasets, and variation with predicted functional consequence is more likely to be homozygous than in other populations, with consequent implications for medical genomics2. Our results show that Indigenous Australians are not a single homogeneous genetic group and their genetic relationship with the peoples of New Guinea is not uniform. These patterns imply that the full breadth of Indigenous Australian genetic diversity remains uncharacterized, potentially limiting genomic medicine and equitable healthcare for Indigenous Australians.

Genetic continuity and change among the Indigenous peoples of California.

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.

A new avialan theropod from an emerging Jurassic terrestrial fauna.

Birds are descended from non-avialan theropod dinosaurs of the Late Jurassic period, but the earliest phase of this evolutionary process remains unclear owing to the exceedingly sparse and spatio-temporally restricted fossil record1-5. Information about the early-diverging species along the avialan line is crucial to understand the evolution of the characteristic bird bauplan, and to reconcile phylogenetic controversies over the origin of birds3,4. Here we describe one of the stratigraphically youngest and geographically southernmost Jurassic avialans, Fujianvenator prodigiosus gen. et sp. nov., from the Tithonian age of China. This specimen exhibits an unusual set of morphological features that are shared with other stem avialans, troodontids and dromaeosaurids, showing the effects of evolutionary mosaicism in deep avialan phylogeny. F. prodigiosus is distinct from all other Mesozoic avialan and non-avialan theropods in having a particularly elongated hindlimb, suggestive of a terrestrial or wading lifestyle-in contrast with other early avialans, which exhibit morphological adaptations to arboreal or aerial environments. During our fieldwork in Zhenghe where F. prodigiosus was found, we discovered a diverse assemblage of vertebrates dominated by aquatic and semi-aquatic species, including teleosts, testudines and choristoderes. Using in situ radioisotopic dating and stratigraphic surveys, we were able to date the fossil-containing horizons in this locality-which we name the Zhenghe Fauna-to 148-150 million years ago. The diversity of the Zhenghe Fauna and its precise chronological framework will provide key insights into terrestrial ecosystems of the Late Jurassic.

Patrilocality and hunter-gatherer-related ancestry of populations in East-Central Europe during the Middle Bronze Age.

The demographic history of East-Central Europe after the Neolithic period remains poorly explored, despite this region being on the confluence of various ecological zones and cultural entities. Here, the descendants of societies associated with steppe pastoralists form Early Bronze Age were followed by Middle Bronze Age populations displaying unique characteristics. Particularly, the predominance of collective burials, the scale of which, was previously seen only in the Neolithic. The extent to which this re-emergence of older traditions is a result of genetic shift or social changes in the MBA is a subject of debate. Here by analysing 91 newly generated genomes from Bronze Age individuals from present Poland and Ukraine, we discovered that Middle Bronze Age populations were formed by an additional admixture event involving a population with relatively high proportions of genetic component associated with European hunter-gatherers and that their social structure was based on, primarily patrilocal, multigenerational kin-groups.

A genetic history of continuity and mobility in the Iron Age central Mediterranean.

The Iron Age was a dynamic period in central Mediterranean history, with the expansion of Greek and Phoenician colonies and the growth of Carthage into the dominant maritime power of the Mediterranean. These events were facilitated by the ease of long-distance travel following major advances in seafaring. We know from the archaeological record that trade goods and materials were moving across great distances in unprecedented quantities, but it is unclear how these patterns correlate with human mobility. Here, to investigate population mobility and interactions directly, we sequenced the genomes of 30 ancient individuals from coastal cities around the central Mediterranean, in Tunisia, Sardinia and central Italy. We observe a meaningful contribution of autochthonous populations, as well as highly heterogeneous ancestry including many individuals with non-local ancestries from other parts of the Mediterranean region. These results highlight both the role of local populations and the extreme interconnectedness of populations in the Iron Age Mediterranean. By studying these trans-Mediterranean neighbours together, we explore the complex interplay between local continuity and mobility that shaped the Iron Age societies of the central Mediterranean.

Interdisciplinary Analyses of Bronze Age Communities from Western Hungary Reveal Complex Population Histories.

In this study, we report 21 ancient shotgun genomes from present-day Western Hungary, from previously understudied Late Copper Age Baden, and Bronze Age Somogyvár-Vinkovci, Kisapostag, and Encrusted Pottery archeological cultures (3,530-1,620 cal Bce). Our results indicate the presence of high steppe ancestry in the Somogyvár-Vinkovci culture. They were then replaced by the Kisapostag group, who exhibit an outstandingly high (up to ∼47%) Mesolithic hunter-gatherer ancestry, despite this component being thought to be highly diluted by the time of the Early Bronze Age. The Kisapostag population contributed the genetic basis for the succeeding community of the Encrusted Pottery culture. We also found an elevated hunter-gatherer component in a local Baden culture-associated individual, but no connections were proven to the Bronze Age individuals. The hunter-gatherer ancestry in Kisapostag is likely derived from two main sources, one from a Funnelbeaker or Globular Amphora culture-related population and one from a previously unrecognized source in Eastern Europe. We show that this ancestry not only appeared in various groups in Bronze Age Central Europe but also made contributions to Baltic populations. The social structure of Kisapostag and Encrusted Pottery cultures is patrilocal, similarly to most contemporaneous groups. Furthermore, we developed new methods and method standards for computational analyses of ancient DNA, implemented to our newly developed and freely available bioinformatic package. By analyzing clinical traits, we found carriers of aneuploidy and inheritable genetic diseases. Finally, based on genetic and anthropological data, we present here the first female facial reconstruction from the Bronze Age Carpathian Basin.

Extensive pedigrees reveal the social organization of a Neolithic community.

Social anthropology and ethnographic studies have described kinship systems and networks of contact and exchange in extant populations1-4. However, for prehistoric societies, these systems can be studied only indirectly from biological and cultural remains. Stable isotope data, sex and age at death can provide insights into the demographic structure of a burial community and identify local versus non-local childhood signatures, archaeogenetic data can reconstruct the biological relationships between individuals, which enables the reconstruction of pedigrees, and combined evidence informs on kinship practices and residence patterns in prehistoric societies. Here we report ancient DNA, strontium isotope and contextual data from more than 100 individuals from the site Gurgy 'les Noisats' (France), dated to the western European Neolithic around 4850-4500 BC. We find that this burial community was genetically connected by two main pedigrees, spanning seven generations, that were patrilocal and patrilineal, with evidence for female exogamy and exchange with genetically close neighbouring groups. The microdemographic structure of individuals linked and unlinked to the pedigrees reveals additional information about the social structure, living conditions and site occupation. The absence of half-siblings and the high number of adult full siblings suggest that there were stable health conditions and a supportive social network, facilitating high fertility and low mortality5. Age-structure differences and strontium isotope results by generation indicate that the site was used for just a few decades, providing new insights into shifting sedentary farming practices during the European Neolithic.

Early contact between late farming and pastoralist societies in southeastern Europe.

Archaeogenetic studies have described two main genetic turnover events in prehistoric western Eurasia: one associated with the spread of farming and a sedentary lifestyle starting around 7000-6000 BC (refs. 1-3) and a second with the expansion of pastoralist groups from the Eurasian steppes starting around 3300 BC (refs. 4,5). The period between these events saw new economies emerging on the basis of key innovations, including metallurgy, wheel and wagon and horse domestication6-9. However, what happened between the demise of the Copper Age settlements around 4250 BC and the expansion of pastoralists remains poorly understood. To address this question, we analysed genome-wide data from 135 ancient individuals from the contact zone between southeastern Europe and the northwestern Black Sea region spanning this critical time period. While we observe genetic continuity between Neolithic and Copper Age groups from major sites in the same region, from around 4500 BC on, groups from the northwestern Black Sea region carried varying amounts of mixed ancestries derived from Copper Age groups and those from the forest/steppe zones, indicating genetic and cultural contact over a period of around 1,000 years earlier than anticipated. We propose that the transfer of critical innovations between farmers and transitional foragers/herders from different ecogeographic zones during this early contact was integral to the formation, rise and expansion of pastoralist groups around 3300 BC.

Northwest African Neolithic initiated by migrants from Iberia and Levant.

In northwestern Africa, lifestyle transitioned from foraging to food production around 7,400 years ago but what sparked that change remains unclear. Archaeological data support conflicting views: (1) that migrant European Neolithic farmers brought the new way of life to North Africa1-3 or (2) that local hunter-gatherers adopted technological innovations4,5. The latter view is also supported by archaeogenetic data6. Here we fill key chronological and archaeogenetic gaps for the Maghreb, from Epipalaeolithic to Middle Neolithic, by sequencing the genomes of nine individuals (to between 45.8- and 0.2-fold genome coverage). Notably, we trace 8,000 years of population continuity and isolation from the Upper Palaeolithic, via the Epipaleolithic, to some Maghrebi Neolithic farming groups. However, remains from the earliest Neolithic contexts showed mostly European Neolithic ancestry. We suggest that farming was introduced by European migrants and was then rapidly adopted by local groups. During the Middle Neolithic a new ancestry from the Levant appears in the Maghreb, coinciding with the arrival of pastoralism in the region, and all three ancestries blend together during the Late Neolithic. Our results show ancestry shifts in the Neolithization of northwestern Africa that probably mirrored a heterogeneous economic and cultural landscape, in a more multifaceted process than observed in other regions.

What Ancient Egyptian Medicine Can Teach Us.

Dr Elsayad describes his impressions regarding the medical and surgical procedures used for patients with cancer and reports on the oncologic cases from ancient Egyptian remains published in the literature.