Historical Y. pestis Genomes Reveal the European Black Death as the Source of Ancient and Modern Plague Pandemics

Abstract

Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300-1420 cal AD), Bolgar City, Russia (1362-1400 AD), and Ellwangen, Germany (1485-1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct.

Ancient pathogen genomics as an emerging tool for infectious disease research

“…Initial analy sis of Y. pestis via PCR from victims of the Black Death revealed a distinct phylogenetic positioning of two mid tolate14th century strains and led to the proposal that the disease entered the continent through independent pulses 64 . By contrast, whole genome analysis of ancient strains from western, northern and southern Europe demonstrated a lack of Y. pestis diversity during the Black Death, which suggests its fast spread through the continent and favours a single wave entry model of the bacterium into Europe 20,30,38 , although the possible presence of additional strain diversity during that time has recently been explored 30 . Intriguingly, the phylo genetic positioning of the Black Death Y. pestis genomes places them on branch 1, only two nucleotide substitu tions away from the 'star like' diversification of branches 1-4 ( Fig.…”

“…Pathogen aDNA is thought to be preserved within the remnants of the pulp chamber, likely as part of desiccated blood 8,17 . Consequently, tooth sampling has proved successful in the retrieval of whole genomes or genome wide data (that is, low coverage genomes that have provided limited analytical resolution) from ancient bacteria such as Y. pestis 20,[30][31][32][33][34][35][36][37][38][39] , Borrelia recurrentis 40 and Salmonella enterica 41 ; ancient eukaryotic pathogens such as Plasmodium falciparum 42 ; and ancient viruses such as hepatitis B virus (HBV) 43,44 and human parvovirus B19 (B19V) 45 . Even M. leprae, which commonly manifests in the chronic form, has been retrieved from ancient teeth 27,28 .…”

“…detection 66 , whereby probes are designed to represent unique or conserved regions from a range of pathogenic bacteria, parasites or viruses. Although amplification based or fluorescence based approaches can be fast and cost effective for screening large sample collections 17,38 , enrichment based techniques are usually coupled with NGS and therefore provide data that can be used to assess aDNA authenticity.…”

“…Intriguingly, the phylo genetic positioning of the Black Death Y. pestis genomes places them on branch 1, only two nucleotide substitu tions away from the 'star like' diversification of branches 1-4 ( Fig. 6), which gave rise to most of the strain diversity identified around the world today 38,130 .…”

How old are bacterial pathogens?

“…One SNP further along branch 1 are the populations 1.PRE2 (London, 1362-1400 [36] and the related low-resolution genotype found in Berg-Op-Zoom, The Netherlands from the fourteenth century [37]; green). One further SNP down the branch is a short branch leading to a genome from Western Asia (1.PRE3; Bolgar City, Tatarstan, Russia; light blue) [34]. Branch 0 begins with ancient genomes from the teeth of Bronze-age individuals who died up to 5000 years ago [31] (populations 0.PRE1, 0.PRE2).…”