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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

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

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

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.