2-AIN-506, 2-AIN-252: Seminar in Bioinformatics (2), (4)
Summer 2024

Jennifer Klunk, Tauras P. Vilgalys, Christian E. Demeure, Xiaoheng Cheng, Mari Shiratori, Julien Madej, Remi Beau, Derek Elli, Maria I. Patino, Rebecca Redfern, Sharon N. DeWitte, Julia A. Gamble, Jesper L. Boldsen, Ann Carmichael, Nukhet Varlik, Katherine Eaton, Jean-Christophe Grenier, G. Brian Golding, Alison Devault, Jean-Marie Rouillard, Vania Yotova, Renata Sindeaux, Chun Jimmie Ye, Matin Bikaran, Anne Dumaine, Jessica F. Brinkworth, Dominique Missiakas, Guy A. Rouleau, Matthias Steinrucken, Javier Pizarro-Cerda, Hendrik N. Poinar, Luis B. Barreiro. Evolution of immune genes is associated with the Black Death. Nature, 611(7935):312-319. 2022. See also follow-up discussion Barton A. R. et al. .

Download preprint: not available

Download from publisher: https://doi.org/10.1038/s41586-022-05349-x PubMed

Related web page: not available

Bibliography entry: BibTeX


Infectious diseases are among the strongest selective pressures driving human 
evolution(1,2). This includes the single greatest mortality event in recorded 
history, the first outbreak of the second pandemic of plague, commonly called the 
Black Death, which was caused by the bacterium Yersinia pestis(3). This pandemic 
devastated Afro-Eurasia, killing up to 30-50% of the population(4). To identify 
loci that may have been under selection during the Black Death, we characterized 
genetic variation around immune-related genes from 206 ancient DNA extracts, 
stemming from two different European populations before, during and after the 
Black Death. Immune loci are strongly enriched for highly differentiated sites 
relative to a set of non-immune loci, suggesting positive selection. We identify 
245 variants that are highly differentiated within the London dataset, four of 
which were replicated in an independent cohort from Denmark, and represent the 
strongest candidates for positive selection. The selected allele for one of these 
variants, rs2549794, is associated with the production of a full-length (versus 
truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and 
increased ability to control intracellular Y. pestis in macrophages. Finally, we 
show that protective variants overlap with alleles that are today associated with 
increased susceptibility to autoimmune diseases, providing empirical evidence for 
the role played by past pandemics in shaping present-day susceptibility to