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Pré-Publication, Document De Travail Année : 2023

Reply to Barton et al: signatures of natural selection during the Black Death

Tauras P Vilgalys
Christian E Demeure
Julien Madej
  • Fonction : Auteur
Rémi Beau
  • Fonction : Auteur
Derek Elli
  • Fonction : Auteur
Rebecca Redfern
  • Fonction : Auteur
Julia A Gamble
Ann Carmichael
Jean-Christophe Grenier
Vania Yotova
Renata Sindeaux
Chun Jimmie Ye
Javier Pizarro-Cerdá

Résumé

Barton et al . raise several statistical concerns regarding our original analyses 2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high F ST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2×10 −5 ), falling below the Bonferroni-corrected significance threshold recommended by Barton et al . Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.
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pasteur-04585452 , version 1 (23-05-2024)

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Tauras P Vilgalys, Jennifer Klunk, Christian E Demeure, Xiaoheng Cheng, Mari Shiratori, et al.. Reply to Barton et al: signatures of natural selection during the Black Death. 2024. ⟨pasteur-04585452⟩

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