The population genomic legacy of the second plague pandemic

Shyam Gopalakrishnan*, S Sunna Ebenesersdóttir, Inge K C Lundstrøm, Gordon Turner-Walker, Kristjan H S Moore, Pierre Luisi, Ashot Margaryan, Michael D Martin, Martin Rene Ellegaard, Ólafur Þ Magnússon, Ásgeir Sigurðsson, Steinunn Snorradóttir, Droplaug N Magnúsdóttir, Jason E Laffoon, Lucy van Dorp, Xiaodong Liu, Ida Moltke, María C Ávila-Arcos, Joshua G Schraiber, Simon RasmussenDavid Juan, Pere Gelabert, Toni de-Dios, Anna K Fotakis, Miren Iraeta-Orbegozo, Åshild J Vågene, Sean Dexter Denham, Axel Christophersen, Hans K Stenøien, Filipe G Vieira, Shanlin Liu, Torsten Günther, Toomas Kivisild, Ole Georg Moseng, Birgitte Skar, Christina Cheung, Marcela Sandoval-Velasco, Nathan Wales, Hannes Schroeder, Paula F Campos, Valdís B Guðmundsdóttir, Thomas Sicheritz-Ponten, Bent Petersen, Jostein Halgunset, Edmund Gilbert, Gianpiero L Cavalleri, Eivind Hovig, Ingrid Kockum, Tomas Olsson, Lars Alfredsson, Thomas F Hansen, Thomas Werge, Eske Willerslev, Francois Balloux, Tomas Marques-Bonet, Carles Lalueza-Fox, Rasmus Nielsen, Kári Stefánsson, Agnar Helgason, M Thomas P Gilbert

*Corresponding author for this work
1 Citation (Scopus)


Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.

Original languageEnglish
JournalCurrent Biology
Issue number21
Pages (from-to)4743-4751.e6
Publication statusPublished - 7 Nov 2022


  • Genome, Bacterial
  • Humans
  • Metagenomics
  • Pandemics/history
  • Phylogeny
  • Plague/epidemiology
  • second plague pandemic
  • population replacement
  • pandemic genomics
  • population genomics
  • plague
  • Yersinia pestis
  • selection
  • Trondheim


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