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.

Undergraduate students (n = 102) were given the Community Attitudes Toward the Mentally I11 (CAMI) questionnaire. Significant differences emerged on 3 of the 4 subscales, based on the participants' ranking of their primary source of information about mental illness. Individuals who reported receiving their information primarily from the electronic media reported less tolerance.

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The ability to sequence genomes from ancient biological material has provided a rich source of information for evolutionary biology and engaged considerable public interest. Although most studies of ancient genomes have focused on vertebrates, particularly archaic humans, newer technologies allow the capture of microbial pathogens and microbiomes from ancient and historical human and non-human remains. This coming of age has been made possible by techniques that allow the preferential capture and amplification of discrete genomes from a background of predominantly host and environmental DNA. There are now near-complete ancient genome sequences for three pathogens of considerable historical interest-premodern bubonic plague (Yersinia pestis), smallpox (Variola virus) and cholera (Vibrio cholerae)-and for three equally important endemic human disease agents-Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy) and Treponema pallidum pallidum (syphilis). Genomic data from these pathogens have extended earlier work by paleopathologists. There have been efforts to sequence the genomes of additional ancient pathogens, with the potential to broaden our understanding of the infectious disease burden common to past populations from the Bronze Age to the early 20 th century. In this review we describe the state-of-the-art of this rapidly developing field, highlight the contributions of ancient pathogen genomics to multidisciplinary endeavors and describe some of the limitations in resolving questions about the emergence and long-term evolution of pathogens.

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What disease or diseases caused the recurrent, demographically punishing epidemics that Europeans called plague? During the last twenty years a once prevalent historical consensus about causes and consequences of European plagues has dissolved, prompting new archival research as well as novel technological and interdisciplinary approaches to material evidence. The core debates about the history of plague are not, however, limited to scholars of medieval and early modern Europe. Molecular biologists over the last decade have determined that the organism that causes plague today, Yersinia pestis, is a relatively recent emergent pathogen descended from a significantly less lethal gastro-intestinal parasite, Yersinia pseudotuberculosis. Furthermore, fifty years ago microbiologists accepted a model of three different ''biovars''-biochemically different variants-of Yersinia pestis, which were tidily aligned to three historical pandemic waves: antiqua, mediaevalis, and orientalis. That synthesis, too, is seriously challenged. There are instead at least eight Yersinia pestis strains and four biovars, and all have emerged within the last 5000 to 20,000 years. 1 This organism remains a likely perpetrator of the great plagues in Europe because all Yersinia pestis biovars can be extraordinarily lethal in human bodies. Most medievalists, including those who doubt that the Black Death and subsequent plagues could have been caused by Yersinia pestis, make a modern assumption that the Black Death indeed had some unique microbial cause. No one yet has argued in a sustained fashion that the plague was a ''perfect storm'' of many different epidemic infectious diseases, but one could. 2 Nor has a radical scepticism emerged-for example, that the causes of each and every local or regional epidemic called peste/pestilentia by contemporaries need to be investigated separately, unrelated to other local contexts-but that, too, might be possible. If we would be truly rigorous, we cannot assume that a ''plague'' in one place was due to the same specific microbial cause as a pestilence in another locality, even

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