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Ludwig van Beethoven (1770–1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public. Medical biographers have since proposed numerous hypotheses, including many substantially heritable conditions. Here we attempt a genomic analysis of Beethoven in order to elucidate potential underlying genetic and infectious causes of his illnesses. We incorporated improvements in ancient DNA methods into existing protocols for ancient hair samples, enabling the sequencing of high-coverage genomes from small quantities of historical hair. We analyzed eight independently sourced locks of hair attributed to Beethoven, five of which originated from a single European male. We deemed these matching samples to be almost certainly authentic and sequenced Beethoven’s genome to 24-fold genomic coverage. Although we could not identify a genetic explanation for Beethoven's hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease. Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven’s severe liver disease, which culminated in his death. Unexpectedly, an analysis of Y chromosomes sequenced from five living members of the Van Beethoven patrilineage revealed the occurrence of an extra-pair paternity event in Ludwig van Beethoven’s patrilineal ancestry. Introduction Results - Authentication of hair samples - Genetic variants associated with somatic disease - Hepatitis B virus DNA recovered from Beethoven’s hair Discussion - Authenticity of Beethoven’s genome - Comparison with living individuals’ genomes - Origins of Beethoven’s diseases - Hepatitis B virus DNA in Beethoven’s hair - Future directions

The Neolithic and Bronze Ages were highly transformative periods for the genetic history of Europe but for the Aegean—a region fundamental to Europe’s prehistory—the biological dimensions of cultural transitions have been elucidated only to a limited extent so far. We have analysed newly generated genome-wide data from 102 ancient individuals from Crete, the Greek mainland and the Aegean Islands, spanning from the Neolithic to the Iron Age. We found that the early farmers from Crete shared the same ancestry as other contemporaneous Neolithic Aegeans. In contrast, the end of the Neolithic period and the following Early Bronze Age were marked by ‘eastern’ gene flow, which was predominantly of Anatolian origin in Crete. Confirming previous findings for additional Central/Eastern European ancestry in the Greek mainland by the Middle Bronze Age, we additionally show that such genetic signatures appeared in Crete gradually from the seventeenth to twelfth centuries bc, a period when the influence of the mainland over the island intensified. Biological and cultural connectedness within the Aegean is also supported by the finding of consanguineous endogamy practiced at high frequencies, unprecedented in the global ancient DNA record. Our results highlight the potential of archaeogenomic approaches in the Aegean for unravelling the interplay of genetic admixture, marital and other cultural practices. Results - The archaeogenetic dataset - Transregional genetic entanglements of Aegean populations - Neolithic to Early/Middle Bronze Age - Mobility in the Middle/Late Bronze Age Aegean - Insights into sex bias, biological kinship and marital practices Discussion Methods - Preparation of aDNA analysis - Analysis of population structure - Admixture analysis with ADMIXTOOLS - Admixture dating - Analysis of biological relatedness - Analysis of ROH - Direct AMS radiocarbon dating

Objectives Family relationship is a key to understand the structure of past societies but its archeological reconstruction mostly stays circumstantial. Archaeogenetic information, especially genome-wide data, provide an objective approach to accurately reconstruct the familial relationship of ancient individuals, thus allowing a robust test of an archaeology-driven hypothesis of kinship. In this study, we applied this approach to disentangle the genetic relationship of early Medieval individuals from Korea, who were secondarily co-buried in a single jar coffin. Materials and Methods We obtained genome-wide data of six early Medieval Korean individuals from a jar coffin. We inferred the genetic relatedness between these individuals and characterized their genetic profiles using well-established population genetics methods. Results Congruent with the unusual pattern of multiple individuals in a single jar coffin, genome-wide analysis of these individuals shows that they form an extended family, including a couple, their two children and both paternal and maternal relatives. We show that these early Medieval Koreans have a genetic profile similar to present-day Koreans. Discussion We show that an unusual case of the secondary multiple burial in a single jar coffin reflects family relationship among the co-buried individuals. We find both paternal and maternal relatives co-buried with the nuclear family, which may suggest a family structure with limited gender bias. We find the genetic profile of early Medieval Koreans similar to that of present-day Koreans, showing that the genetic root of the present-day Koreans goes back at least 1500?years in the Korean peninsula. 1 Introduction 2 Materials and methods 2.1 Archeological context of the Gunsan jar coffin 2.2 Permission for destructive analyses of skeletal elements 2.3 Skeletal analysis 2.4 Sampling of skeletal materials 2.5 Ancient DNA laboratory work and sequencing 2.6 Ancient DNA sequencing data processing and authentication 2.7 Reprocessing of whole genome sequences of present-day Koreans 2.8 Data set compilation 2.9 Principal component analysis 2.10 Genetic kinship analysis 2.11 Runs of homozygosity analysis 2.12 F-statistics and qpWave/qpAdm analysis 3 Results 3.1 | Ancient genome-wide data production 3.2 | A familial relationship of individuals from a single jar coffin 3.3 | The genetic profile of early medieval Koreans 4 Discussion

It has been hypothesized that the Neolithic transition towards an agricultural and pastoralist economy facilitated the emergence of human adapted pathogens. Here, we recovered eight Salmonella enterica subsp. enterica genomes from human skeletons of transitional foragers, pastoralists, and agro-pastoralists in western Eurasia that were up to 6,500 years old. Despite the high genetic diversity of S. enterica all ancient bacterial genomes clustered in a single previously uncharacterized branch that contains S. enterica adapted to multiple mammalian species. All ancient bacterial genomes from prehistoric (agro-)pastoralists fall within a part of this branch that also includes the human-specific S. enterica Paratyphi C, illustrating the evolution of a human pathogen over a period of five thousand years. Bacterial genomic comparisons suggest that the earlier ancient strains were not host specific, differed in pathogenic potential, and experienced convergent pseudogenization that accompanied their downstream host adaptation. These observations support the concept that the emergence of human adapted S. enterica is linked to human cultural transformations.

Here, we report genome-wide data analyses from 110 ancient Near Eastern individuals spanning the Late Neolithic to Late Bronze Age, a period characterized by intense interregional interactions for the Near East. We find that 6th millennium BCE populations of North/Central Anatolia and the Southern Caucasus shared mixed ancestry on a genetic cline that formed during the Neolithic between Western Anatolia and regions in today’s Southern Caucasus/Zagros. During the Late Chalcolithic and/or the Early Bronze Age, more than half of the Northern Levantine gene pool was replaced, while in the rest of Anatolia and the Southern Caucasus, we document genetic continuity with only transient gene flow. Additionally, we reveal a genetically distinct individual within the Late Bronze Age Northern Levant. Overall, our study uncovers multiple scales of population dynamics through time, from extensive admixture during the Neolithic period to long-distance mobility within the globalized societies of the Late Bronze Age. Video Abstract - Introduction - Results -- Sample Corpus and Data Compilation -- The Late Neolithic/Early Chalcolithic Genetic Structure in Anatolia, Northern Levant, and Caucasian Lowlands -- Neolithic Admixture and a Common Genetic Profile of Chalcolithic and Bronze Age Groups -- Admixture Modeling of the Chalcolithic and Bronze Age Groups -- Genetic Turnover in the Bronze Age Northern Levant -- Evidence for Individual Mobility in Alalakh - Discussion -- Genetic Homogenization across Anatolia and the Southern Caucasus prior to the Bronze Age -- Population and Territorial State Dynamics in the Northern Levant -- Conclusions STAR★Methods

Southern Italy is a key region for understanding the agricultural transition in the Mediterranean due to its central position. We present a genomic transect for 19 prehistoric Sicilians that covers the Early Mesolithic to Early Neolithic period. We find that the Early Mesolithic hunter-gatherers (HGs) are a highly drifted sister lineage to Early Holocene western European HGs, whereas a quarter of the Late Mesolithic HGs ancestry is related to HGs from eastern Europe and the Near East. This indicates substantial gene flow from (south-)eastern Europe between the Early and Late Mesolithic. The Early Neolithic farmers are genetically most similar to those from the Balkan and Greece, and carry only a maximum of ∼7% ancestry from Sicilian Mesolithic HGs. Ancestry changes match changes in dietary profile and material culture, except for two individuals who may provide tentative initial evidence that HGs adopted elements of farming in Sicily.One-sentence summaryGenome-wide and isotopic data from prehistoric Sicilians reveal a pre-farming connection to (south-) eastern Europe, and tentative initial evidence that hunter-gatherers adopted some Neolithic aspects prior to near-total replacement by early farmers.

Bronze and Iron Age genomes suggest a European-related gene flow coincided with the Philistines arrival in ancient Ashkelon., The ancient Mediterranean port city of Ashkelon, identified as “Philistine” during the Iron Age, underwent a marked cultural change between the Late Bronze and the early Iron Age. It has been long debated whether this change was driven by a substantial movement of people, possibly linked to a larger migration of the so-called “Sea Peoples.” Here, we report genome-wide data of 10 Bronze and Iron Age individuals from Ashkelon. We find that the early Iron Age population was genetically distinct due to a European-related admixture. This genetic signal is no longer detectible in the later Iron Age population. Our results support that a migration event occurred during the Bronze to Iron Age transition in Ashkelon but did not leave a long-lasting genetic signature.

Ancient DNA informs on past culturesArchaeology has used analysis of the artifacts and remains of people to uncover their past behaviors and to infer their cultural practices. However, establishing genetic relationships has only recently become possible. Mittniket al.examined the kinship and inheritance of the remains of people from the German Lech River Valley over a time period spanning the Late Neolithic Corded Ware Culture, the Bell Beaker Complex, the Early Bronze Age, and the Middle Bronze Age (see the Perspective by Feinman and Neitzel). From genetic and archaeological analyses, it was revealed that the Early Bronze Age household's burials over multiple generations consisted of a high-status core family and unrelated low-status individuals. Furthermore, women were not related to the men within the household, suggesting that men stayed within their birth communities in this society, but women did not.Science, this issue p.731; see also p.682

Since the Bronze Age, pastoralism has been a dominant subsistence mode on the Western steppe, but the origins of this tradition on the Eastern steppe are poorly understood. Here we investigate a putative early pastoralist population in northern Mongolia and find that dairy production was established on the Eastern steppe by 1300 BCE. Milk proteins preserved in dental calculus indicate an early focus on Western domesticated ruminants rather than local species, but genetic ancestry analysis indicates minimal admixture with Western steppe herders, suggesting that dairy pastoralism was introduced through adoption by local hunter-gatherers rather than population replacement.Recent paleogenomic studies have shown that migrations of Western steppe herders (WSH) beginning in the Eneolithic (ca. 3300–}2700 BCE) profoundly transformed the genes and cultures of Europe and central Asia. Compared with Europe, however, the eastern extent of this WSH expansion is not well defined. Here we present genomic and proteomic data from 22 directly dated Late Bronze Age burials putatively associated with early pastoralism in northern Mongolia (ca. 1380{–975 BCE). Genome-wide analysis reveals that they are largely descended from a population represented by Early Bronze Age hunter-gatherers in the Baikal region, with only a limited contribution (˜7%) of WSH ancestry. At the same time, however, mass spectrometry analysis of dental calculus provides direct protein evidence of bovine, sheep, and goat milk consumption in seven of nine individuals. No individuals showed molecular evidence of lactase persistence, and only one individual exhibited evidence of gt;10% WSH ancestry, despite the presence of WSH populations in the nearby Altai-Sayan region for more than a millennium. Unlike the spread of Neolithic farming in Europe and the expansion of Bronze Age pastoralism on the Western steppe, our results indicate that ruminant dairy pastoralism was adopted on the Eastern steppe by local hunter-gatherers through a process of cultural transmission and minimal genetic exchange with outside groups.