Search

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

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