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.
Subject(s)
Deafness , Famous Persons , Music , Male , Humans , Genetic Predisposition to Disease , Genomics , HairABSTRACT
Understanding and quantifying populations' adaptive genetic variation and their response to climate change are critical to reforestation's seed source selection, forest management decisions, and gene conservation. Landscape genomics combined with geographic and environmental information provide an opportunity to interrogate forest populations' genome-wide variation for understanding the extent to which evolutionary forces shape past and contemporary populations' genetic structure, and identify those populations that may be most at risk under future climate change. Here, we used genotyping by sequencing to generate over 11,000 high-quality variants from Platycladus orientalis range-wide collection to evaluate its diversity and to predict genetic offset under future climate scenarios. Platycladus orientalis is a widespread conifer in China with significant ecological, timber, and medicinal values. We found population structure and evidences of isolation by environment, indicative of adaptation to local conditions. Gradient forest modeling identified temperature-related variables as the most important environmental factors influencing genetic variation and predicted areas with higher risk under future climate change. This study provides an important reference for forest resource management and conservation for P. orientalis.