ERP127243 PRJEB43291 ena-STUDY-CNRS UMR 5288-24-02-2021-14:44:49:110-1266 No particular genomic features underpin the dramatic economic consequences of 17th century plague epidemics in Italy The second plague pandemic started with the Black Death, an infection caused by a Yersinia pestis strain that killed approximately 30-60% of the European population in the mid-14th century. Since then, several epidemic waves came back to haunt human populations until the 18th century, when this pathogenic form vanished. During the 17th century, plague only added to an already long list of various scourges, including global climate cooling, poor harvests and famines, as well as plunder and wars. At the time, plague had a stronger demographic toll on populations from southern Europe, especially Italy, where it caused long-lasting economical damage. It remains, however, unknown whether sanitation control of the epidemic and its animal vectors was less effective there, or whether more harmful pathogenic strains circulated. Screening the DNA content of 26 human bodies excavated from the 1629-1630 plague cemetery of Lariey (French Alps), we identified two tooth remains particularly rich in plague genetic material. Further sequencing revealed two Y. pestis genomes phylogenetically closest to those previously characterized from the 1636 plague outbreak of San Procolo a Saturno, Italy. They both belonged to a larger cluster extending from the Alps to northern Germany, that was contemporary to and probably propagated during the Thirty Years war (1618-1648). Patterns of sequence variation did not support faster evolutionary rates in the Italian genomes and instead revealed only rare private non-synonymous mutations, which did not affect virulence genes. This, and the limited spread of such genomes outside of Italy, suggest environmental, social and/or institutional rather than biological causes for the severe Italian epidemic trajectory observed during the 17th century. 17th century CE Plague genomes from the French Alps site of Lariey The second plague pandemic started with the Black Death, an infection caused by a Yersinia pestis strain that killed approximately 30-60% of the European population in the mid-14th century. Since then, several epidemic waves came back to haunt human populations until the 18th century, when this pathogenic form vanished. During the 17th century, plague only added to an already long list of various scourges, including global climate cooling, poor harvests and famines, as well as plunder and wars. At the time, plague had a stronger demographic toll on populations from southern Europe, especially Italy, where it caused long-lasting economical damage. It remains, however, unknown whether sanitation control of the epidemic and its animal vectors was less effective there, or whether more harmful pathogenic strains circulated. Screening the DNA content of 26 human bodies excavated from the 1629-1630 plague cemetery of Lariey (French Alps), we identified two tooth remains particularly rich in plague genetic material. Further sequencing revealed two Y. pestis genomes phylogenetically closest to those previously characterized from the 1636 plague outbreak of San Procolo a Saturno, Italy. They both belonged to a larger cluster extending from the Alps to northern Germany, that was contemporary to and probably propagated during the Thirty Years war (1618-1648). Patterns of sequence variation did not support faster evolutionary rates in the Italian genomes and instead revealed only rare private non-synonymous mutations, which did not affect virulence genes. This, and the limited spread of such genomes outside of Italy, suggest environmental, social and/or institutional rather than biological causes for the severe Italian epidemic trajectory observed during the 17th century. Ancient DNA Plague genomes Second plague pandemics 17th century CE Thirty Years War ENA-FIRST-PUBLIC 2021-04-01 ENA-LAST-UPDATE 2021-02-24