Genomic analyses of hair from Ludwig van Beethoven

Tristan James Alexander Begg¹, Axel Schmidt², Arthur Kocher³, Maarten H D Larmuseau⁴, Göran Runfeldt⁵, Paul Andrew Maier⁵, John D Wilson⁶, Rodrigo Barquera⁷, Carlo Maj⁸, András Szolek⁹, Michael Sager⁵, Stephen Clayton¹⁰, Alexander Peltzer¹¹, Ruoyun Hui¹², Julia Ronge¹³, Ella Reiter¹⁴, Cäcilia Freund¹⁵, Marta Burri¹⁵, Franziska Aron¹⁵, Anthi Tiliakou¹⁶, Joanna Osborn¹⁷, Doron M Behar¹⁸, Malte Boecker¹³, Guido Brandt¹⁵, Isabelle Cleynen¹⁹, Christian Strassburg²⁰, Kay Prüfer⁷, Denise Kühnert²¹, William Rhea Meredith²², Markus M Nöthen², Robert David Attenborough²³, Toomas Kivisild²⁴, Johannes Krause²⁵

Affiliations

¹ Department of Archaeology, University of Cambridge, CB2 3ER Cambridge, UK; Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany. Electronic address: tristanj.a.begg@gmail.com.
² Institute of Human Genetics, University Hospital of Bonn, Bonn 53127, Germany.
³ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Transmission, Infection, Diversification and Evolution Group, Max Planck Institute for the Science of Human History, 07745 Jena, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
⁴ Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Laboratory of Human Genetic Genealogy, Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; ARCHES - Antwerp Cultural Heritage Sciences, Faculty of Design Sciences, University of Antwerp, 2000 Antwerp, Belgium; Histories vzw, 9000 Gent, Belgium.
⁵ FamilyTreeDNA, Gene by Gene, Houston, TX 77008, USA.
⁶ Austrian Academy of Sciences, 1030 Vienna, Austria; University of Vienna, 1010 Vienna, Austria.
⁷ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany.
⁸ Institute of Human Genetics, University Hospital of Bonn, Bonn 53127, Germany; Center for Human Genetics, University Hospital of Marburg, Marburg, Germany.
⁹ Applied Bioinformatics, Department for Computer Science, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
¹⁰ Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
¹¹ Quantitative Biology Center (QBiC) University of Tübingen, Tübingen, Germany.
¹² MacDonald Institute for Archaeological Research, University of Cambridge, Cambridge CB2 3ER, UK; Alan Turing Institute, 2QR, John Dodson House, London NW1 2DB, UK.
¹³ Beethoven-Haus Bonn, 53111 Bonn, Germany.
¹⁴ Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany.
¹⁵ Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
¹⁶ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
¹⁷ Department of Archaeology, University of Cambridge, CB2 3ER Cambridge, UK.
¹⁸ Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
¹⁹ Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
²⁰ Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany.
²¹ Transmission, Infection, Diversification and Evolution Group, Max Planck Institute for the Science of Human History, 07745 Jena, Germany; European Virus Bioinformatics Center (EVBC), Jena, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
²² American Beethoven Society, San Jose State University, San Jose, CA 95192, USA; Ira F. Brilliant Center for Beethoven Studies, San Jose State University, San Jose, CA 95192, USA; School of Music and Dance, San Jose State University, San Jose, CA 95192, USA.
²³ MacDonald Institute for Archaeological Research, University of Cambridge, Cambridge CB2 3ER, UK; School of Archaeology & Anthropology, Australian National University, Canberra, ACT 0200, Australia.
²⁴ Department of Archaeology, University of Cambridge, CB2 3ER Cambridge, UK; Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia. Electronic address: toomas.kivisild@kuleuven.be.
²⁵ Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany; Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany. Electronic address: krause@eva.mpg.de.

PMID: 36958333
DOI: 10.1016/j.cub.2023.02.041

Free article

Genomic analyses of hair from Ludwig van Beethoven

Tristan James Alexander Begg et al. Curr Biol. 2023.

Free article

. 2023 Apr 24;33(8):1431-1447.e22.

doi: 10.1016/j.cub.2023.02.041. Epub 2023 Mar 22.

Authors

Affiliations

¹ Department of Archaeology, University of Cambridge, CB2 3ER Cambridge, UK; Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany. Electronic address: tristanj.a.begg@gmail.com.
² Institute of Human Genetics, University Hospital of Bonn, Bonn 53127, Germany.
³ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Transmission, Infection, Diversification and Evolution Group, Max Planck Institute for the Science of Human History, 07745 Jena, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
⁴ Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Laboratory of Human Genetic Genealogy, Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; ARCHES - Antwerp Cultural Heritage Sciences, Faculty of Design Sciences, University of Antwerp, 2000 Antwerp, Belgium; Histories vzw, 9000 Gent, Belgium.
⁵ FamilyTreeDNA, Gene by Gene, Houston, TX 77008, USA.
⁶ Austrian Academy of Sciences, 1030 Vienna, Austria; University of Vienna, 1010 Vienna, Austria.
⁷ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany.
⁸ Institute of Human Genetics, University Hospital of Bonn, Bonn 53127, Germany; Center for Human Genetics, University Hospital of Marburg, Marburg, Germany.
⁹ Applied Bioinformatics, Department for Computer Science, University of Tübingen, Sand 14, 72076 Tübingen, Germany; Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
¹⁰ Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
¹¹ Quantitative Biology Center (QBiC) University of Tübingen, Tübingen, Germany.
¹² MacDonald Institute for Archaeological Research, University of Cambridge, Cambridge CB2 3ER, UK; Alan Turing Institute, 2QR, John Dodson House, London NW1 2DB, UK.
¹³ Beethoven-Haus Bonn, 53111 Bonn, Germany.
¹⁴ Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany.
¹⁵ Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
¹⁶ Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
¹⁷ Department of Archaeology, University of Cambridge, CB2 3ER Cambridge, UK.
¹⁸ Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
¹⁹ Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
²⁰ Department of Internal Medicine I, University Hospital Bonn, 53127 Bonn, Germany.
²¹ Transmission, Infection, Diversification and Evolution Group, Max Planck Institute for the Science of Human History, 07745 Jena, Germany; European Virus Bioinformatics Center (EVBC), Jena, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany.
²² American Beethoven Society, San Jose State University, San Jose, CA 95192, USA; Ira F. Brilliant Center for Beethoven Studies, San Jose State University, San Jose, CA 95192, USA; School of Music and Dance, San Jose State University, San Jose, CA 95192, USA.
²³ MacDonald Institute for Archaeological Research, University of Cambridge, Cambridge CB2 3ER, UK; School of Archaeology & Anthropology, Australian National University, Canberra, ACT 0200, Australia.
²⁴ Department of Archaeology, University of Cambridge, CB2 3ER Cambridge, UK; Department of Human Genetics, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu 51010, Estonia. Electronic address: toomas.kivisild@kuleuven.be.
²⁵ Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany; Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany; Max Planck Institute for the Science of Human History, Kahlaische Str. 10, 07745 Jena, Germany. Electronic address: krause@eva.mpg.de.

PMID: 36958333
DOI: 10.1016/j.cub.2023.02.041

Abstract

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.

Keywords: Ludwig van Beethoven; ancient DNA; extra-pair paternity; genetic genealogy; genobiography; geo-genetic triangulation; hair; hepatitis B virus; medical genetics; the Beethoven genome project.

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Conflict of interest statement

Declaration of interests T.J.A.B. has received scholarships from the American Beethoven Society in support of his graduate studies. G.R., M.S., and P.A.M. are employees of GeneByGene. G.R. and M.S. hold stock options in MyDNA, Inc. M.M.N. has received fees for membership in an advisory board from HMG Systems Engineering GmbH (Fürth, Germany), for membership in the Medical-Scientific Editorial Office of the Deutsches Ärzteblatt, and for serving as a consultant for EVERIS Belgique SPRL in a project of the European Commission (REFORM/SC2020/029). M.M.N. receives salary payments from Life & Brain GmbH and holds shares in Life & Brain GmbH.

Comment in

Genomic Analysis of Hair From Celebrated Composer Provides Insight Into Liver Disease Susceptibility.
Naimimohasses S, Bhat M. Naimimohasses S, et al. Gastroenterology. 2023 Aug;165(2):514. doi: 10.1053/j.gastro.2023.04.020. Epub 2023 Apr 29. Gastroenterology. 2023. PMID: 37127096 No abstract available.

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Genomic analyses of hair from Ludwig van Beethoven

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Genomic analyses of hair from Ludwig van Beethoven

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Abstract

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