美国芝加哥大学Luis B. Barreiro等研究人员合作发现，免疫基因的演化与黑死病有关。2022年10月19日，《自然》杂志在线发表了这项成果。

为了确定在黑死病期间可能被选择的基因座，研究人员从206个古老的DNA提取物中描述了免疫相关基因的遗传变异，这些基因来自于黑死病之前、期间和之后的两个不同的欧洲人口群体。相对于一组非免疫性位点，免疫性位点的高分化位点被强烈富集，这表明了正向选择。研究人员在伦敦的数据集中发现了245个高度分化的变体，其中4个在丹麦的一个独立队列中被复制，代表了正向选择的最强候选者。其中一个变体rs2549794的选择等位基因与产生全长（相对于截断）的ERAP2转录本、对Y. pestis的细胞因子反应的变化以及在巨噬细胞中控制细胞内Y. pestis的能力增加有关。

最后，研究人员表明，保护性变体与今天与自身免疫性疾病易感性增加有关的等位基因相重叠，为过去的大流行病在塑造今天的疾病易感性方面所起的作用提供了经验性证据。

据悉，传染病是推动人类演化的最强大的选择压力之一。这包括有史以来最大的一次死亡事件，即第二次鼠疫大流行的第一次爆发，通常称为黑死病，它是由鼠疫耶尔森氏杆菌（Yersinia pestis）引起的。这场大流行破坏了非洲-欧亚大陆，造成高达30-50%的人口死亡。

附：英文原文

Title: Evolution of immune genes is associated with the Black Death

Author: Klunk, Jennifer, Vilgalys, Tauras P., Demeure, Christian E., Cheng, Xiaoheng, Shiratori, Mari, Madej, Julien, Beau, Rmi, Elli, Derek, Patino, Maria I., Redfern, Rebecca, DeWitte, Sharon N., Gamble, Julia A., Boldsen, Jesper L., Carmichael, Ann, Varlik, Nkhet, Eaton, Katherine, Grenier, Jean-Christophe, Golding, G. Brian, Devault, Alison, Rouillard, Jean-Marie, Yotova, Vania, Sindeaux, Renata, Ye, Chun Jimmie, Bikaran, Matin, Dumaine, Anne, Brinkworth, Jessica F., Missiakas, Dominique, Rouleau, Guy A., Steinrcken, Matthias, Pizarro-Cerd, Javier, Poinar, Hendrik N., Barreiro, Luis B.

Issue&Volume: 2022-10-19

Abstract: Infectious diseases are among the strongest selective pressures driving human evolution1,2. 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 pestis3. This pandemic devastated Afro-Eurasia, killing up to 30–50% of the population4. 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.

DOI: 10.1038/s41586-022-05349-x

Source: https://www.nature.com/articles/s41586-022-05349-x