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 disease.

Ne pire her biri bir zerk idici div-i hücum Ne pire bilmez aman, vermez aman cana kıyar Pire bir heybet ile halka hücum eyledi kim Div bu yerde eger baglasalar ide firar O'what a flea! Each one is an injecting attack-demon O'what a flea! Has no mercy, shows no mercy, takes life Fleas attacked people with such majesty that Demon would flee this place even tied down 1 3 Handling Y. pestis-infected dead or live animals and eating their meat can transmit the disease to humans.

We are currently experiencing one of the most disruptive pandemics in modern history. The outbreak of COVID-19 that was first recorded in Wuhan, China and quickly spread across the globe has resulted in nearly 5 million confirmed cases to date and more than 300,000 deaths. Where we stand now, it is still uncertain how many it will infect or kill worldwide, how long it will continue, and when-if everlife will return to normal. What we know for sure is that this is a pivotal moment and that we are experiencing a historic event that will transform our societies both profoundly and irreversibly. As we wade into this new age of pandemics, it is critical to rethink how we write the history of pandemics.With a conviction that the past helps us to understand the present and that the present should help us to rethink the past, I turn to the legacy of past plagues. In this essay, I take stock of the lasting legacies of past plagues because they continue to shape the way we think about new pandemics. In particular, I address persistent problems, such as European exceptionalism, triumphalism, and epidemiological Orientalism, that are not only ubiquitous in plague studies, but also staples of public opinion about pandemics, past and present.

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