Over the last few years, genomic studies on Yersinia pestis , the causative agent of all known plague epidemics, have considerably increased in numbers, spanning a period of about 5,000 y. Nonetheless, questions concerning historical reservoirs and routes of transmission remain open. Here, we present and describe five genomes from the second half of the 14th century and reconstruct the evolutionary history of Y. pestis by reanalyzing previously published genomes and by building a comprehensive phylogeny focused on strains attributed to the Second Plague Pandemic (14th to 18th century). Corroborated by historical and ecological evidence, the presented phylogeny, which includes our Y. pestis genomes, could support the hypothesis of an entry of plague into Western European ports through distinct waves of introduction during the Medieval Period, possibly by means of fur trade routes, as well as the recirculation of plague within the human population via trade routes and human movement.

Significance: The spread and evolution of plague have been under debate in the past few years. However, very little is known of the dynamics of the plague pathogen,Yersinia pestis, during the last phase of the Second Plague Pandemic in Europe (18th and 19th century). We present nine ancientY. pestisgenomes from the Second Plague Pandemic. CHE1 is the first Second Plague Pandemic genome from the Caucasus region, an area that houses plague wildlife reservoirs to this day, making it a key strain to help elucidate the origin of Medieval and Early Modern plague. Our study documents the importance of a noneurocentric approach to historical plague dynamics and proposes an origin of plague introductions outside of Europe.

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, infects a majority of adults globally. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups has suggested the virus codiverged with human migrations out of Africa, although a much younger origin has also been proposed. We present three full ancient European HSV-1 genomes and one partial genome, dating from the 3rd to 17th century CE, sequenced to up to 9.5× with paired human genomes up to 10.16×. Considering a dataset of modern and ancient genomes, we apply phylogenetic methods to estimate the age of sampled modern Eurasian HSV-1 diversity to 4.68 (3.87 to 5.65) ka. Extrapolation of estimated rates to a global dataset points to the age of extant sampled HSV-1 as 5.29 (4.60 to 6.12) ka, suggesting HSV-1 lineage replacement coinciding with the late Neolithic period and following Bronze Age migrations.

Background: The human pathogenHaemophilus influenzaewas the main cause of bacterial meningitis in children and a major cause of worldwide infant mortality before the introduction of a vaccine in the 1980s. Although the occurrence of serotype b (Hib), the most virulent type ofH. influenzae, has since decreased, reports of infections with other serotypes and non-typeable strains are on the rise. While non-typeable strains have been studied in-depth, very little is known of the pathogen’s evolutionary history, and no genomes dating prior to 1940 were available.Results: We describe a Hib genome isolated from a 6-year-old Anglo-Saxon plague victim, from approximately 540 to 550 CE, Edix Hill, England, showing signs of invasive infection on its skeleton. We find that the genome clusters in phylogenetic division II with Hib strain NCTC8468, which also caused invasive disease. While the virulence profile of our genome was distinct, its genomic similarity to NCTC8468 points to mostly clonal evolution of the clade since the 6th century. We also reconstruct a partialYersinia pestisgenome, which is likely identical to a published first plague pandemic genome of Edix Hill.Conclusions: Our study presents the earliest genomic evidence forH. influenzae, points to the potential presence of larger genomic diversity in the phylogenetic division II serotype b clade in the past, and allows the first insights into the evolutionary history of this major human pathogen. The identification of both plague and Hib opens questions on the effect of plague in immunocompromised individuals already affected by infectious diseases.

Significance: Louse-borne relapsing fever was one of the major diseases affecting Western human populations, with its last major pandemic killing millions after World War I. Despite the major role fevers have played in epidemic events throughout history, molecular evidence for the presence of their etiological agent has been extremely scarce in historical samples worldwide. By comparing our medievalBorrelia recurrentisgenome with modern representatives of the species, we offer an historical snapshot of genomic changes in an immune-evasion system and of reductive evolution in a specialized vector-borne human pathogen. This shotgun sequencing project highlights the potential for ancient DNA research to uncover pathogens which are undetectable to osteological analysis but are known to have played major roles in European health historically.