Contributors: University of Chicago; McMaster University Hamilton, Ontario; Daicel Arbor Biosciences Ann Arbor, MI; Yersinia; Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047); Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Museum of London; University of South Carolina Columbia; University of Manitoba Winnipeg; University of Southern Denmark (SDU); Indiana University Bloomington; Indiana University System; Rutgers University Newark; Rutgers University System (Rutgers); Université de Montréal (UdeM); University of Michigan Ann Arbor; University of Michigan System; CHU Sainte Justine Montréal; University of California San Francisco (UC San Francisco); University of California (UC); University of Illinois at Urbana-Champaign Urbana (UIUC); University of Illinois System; McGill University = Université McGill Montréal, Canada; This work was supported by grant R01-GM134376 to LBB, HP, and JP-C, a grant from the Wenner-Gren Foundation to JB (8702), and the UChicago DDRCC, Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) (NIDDK P30 DK042086). HNP was supported by an Insight Grant #20008499 from the Social Sciences and Humanities Research Council of Canada (SSHRC) and The Canadian Institute for Advanced Research under the Humans and the Microbiome program. TPV was supported by NIH F32GM140568. XC and MSt were supported by grant R01GM146051.
نبذة مختصرة : 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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