Royal College of Surgeons in Ireland
The population genomic legacy of the second plague pandemic.pdf (3.66 MB)

The population genomic legacy of the second plague pandemic

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journal contribution
posted on 2023-11-15, 16:38 authored by Shyam Gopalakrishnan, Edmund GilbertEdmund Gilbert, Gianpiero CavalleriGianpiero Cavalleri, M Thomas P Gilbert

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%. 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). 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.


Carlsbergfondet grants CF14-0995

Marie Sk1odowska-Curie Actions grant 655732

Danish National Research Foundation grant DNRF94

Lundbeckfonden grant R52-5062

Carlsbergfondet grant CF18-1109

ERC Consolidator grant (681396-ExtinctionGenomics)

MEDHEAL600 funded by the Research Council of Norway (FRIHUMSAM) project number 262424

Science Foundation Ireland under grant number 16/RC/3948

European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 864203)



The original article is available

Published Citation

Gopalakrishnan S. et al. The population genomic legacy of the second plague pandemic. Curr Biol. 2022;32(21):4743-4751.e6

Publication Date

30 September 2022

PubMed ID



  • FutureNeuro Centre
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Neurological and Psychiatric Disorders


Elsevier BV


  • Published Version (Version of Record)