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 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

Research output: Contribution to journalArticlepeer-review

Abstract

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
DOIs
Publication statusAccepted/In press - 15 Sept 2022

Bibliographical note

Funding Information:
We acknowledge the following for funding our research: Carlsbergfondet grants CF14-0995 and Marie Skłodowska-Curie Actions grant 655732 (to S.G.), Danish National Research Foundation grant DNRF94 , Lundbeckfonden grant R52-5062 , Carlsbergfondet grant CF18-1109 and ERC Consolidator grant ( 681396-Extinction Genomics ) (to M.T.P.G.), and MEDHEAL600 funded by the Research Council of Norway (FRIHUMSAM) project number is 262424 . G.L.C. is supported by the Science Foundation Ireland under grant number 16/RC/3948 . T.M.B. is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 864203 ).

Funding Information:
We acknowledge the following for funding our research: Carlsbergfondet grants CF14-0995 and Marie Skłodowska-Curie Actions grant 655732 (to S.G.), Danish National Research Foundation grant DNRF94, Lundbeckfonden grant R52-5062, Carlsbergfondet grant CF18-1109 and ERC Consolidator grant (681396-ExtinctionGenomics) (to M.T.P.G.), and MEDHEAL600 funded by the Research Council of Norway (FRIHUMSAM) project number is 262424. G.L.C. is supported by the Science Foundation Ireland under grant number 16/RC/3948. T.M.B. is supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 864203). The authors would also like to acknowledge support from the Danish National High-Throughput DNA-Sequencing Centre and DTU-Computerome for providing assistance with massively parallel DNA sequencing and computational infrastructure respectively. Designed the study, I.K.C.L. S.G. G.T.-W. A.H. and M.T.P.G.; generated paleogenomic data, I.K.C.L. S.S.E. C.C. A.M. Ó.þ.M. Á.S. D.N.M. S.S. A.F. M.I.-O. and Å.J.V.; analyzed paleogenomic data, S.G. S.S.E. A.H. I.K.C.L. P.L. A.M. M.D.M. M.R.E. L.v.D. K.H.S.M. I.M. M.C.A.-A. J.S. S.R. D.J. P.G. T.d.-D. F.G.V. S.L. T.G. T.K. and X.L.; provided additional computational and laboratory guidance/support, M.S.-V. N.W. H.S. P.F.C. T.S.-P. B.P. F.B. T.M.-B. C.L.-F. R.N. and E.W.; isotopic analyses, J.E.L.; provided archaeological samples and context, G.T.-W. J.E.L. S.D.D. A.C. H.K.S. O.G.M. and B.S.; provided modern reference datasets, K.S. A.H. J.H. V.B.G. E.G. G.C. E.H. I.K. T.O. L.A. T.F.H. and T.W.; wrote the paper, M.T.P.G. S.G. S.S.E. I.K.C.L. and A.H. with input from all other authors. The authors declare no competing interests.

Publisher Copyright:
© 2022 The Authors

Keywords

  • pandemic genomics
  • plague
  • population genomics
  • population replacement
  • second plague pandemic
  • selection
  • Trondheim
  • Yersinia pestis

Cite this