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.

Abstract Evolution relies on the availability of genetic diversity for fitness-based selection. However, most DNA viruses employ DNA polymerases capable of exonucleolytic proofreading to limit mutation rates during DNA replication. The relative genetic stability produced by high fidelity genome replication can make studying DNA virus adaptation and evolution an intensive endeavor, especially in slowly replicating viruses. Here, we present a proofreading impaired polymerase mutant (Y547S) of Marek’s disease virus that exhibits a hypermutator phenotype while maintaining unimpaired growth in vitro and wild-type (WT)-like pathogenicity in vivo. At the same time, mutation frequencies observed in Y547S virus populations are 2–5 fold higher compared to the parental WT virus. We find that Y547S adapts faster to growth in originally non-permissive cells, evades pressure conferred by antiviral inhibitors more efficiently, and is more easily attenuated by serial passage in cultured cells when compared to WT. Our results suggest that hypermutator viruses can serve as a tool to accelerate evolutionary processes and help identify key genetic changes required for adaptation to novel host cells and resistance to antiviral therapy. Similarly, the rapid attenuation achieved through adaption of hypermutators to growth in cell culture enables identification of genetic chances underlying attenuation and virulence, knowledge that could practically exploited, for example in the rational design of vaccines.

Pearl millet is among the top three-cereal production in one of the most climate vulnerable regions, sub-Saharan Africa. Its Sahelian origin makes it adapted to grow in poor sandy soils under low soil water regimes. Pearl millet is thus considered today as one of the most interesting crops to face the global warming. Flowering time, a trait highly correlated with latitude, is one of the key traits that could be modulated to face future global changes. West African pearl millet landraces, can be grouped into early- (EF) and late-flowering (LF) varieties, each flowering group playing a specific role in the functioning and resilience of Sahelian smallholders. The aim of this study was thus to detect genes linked to flowering but also linked to relevant traits within each flowering group. We thus investigated genomic and phenotypic diversity in 109 pearl millet landrace accessions, i.e., 66 early-flowering and 43 late-flowering, grown in the groundnut basin, the first area of rainfed agriculture in Senegal dominated by dry cereals (millet, maize, and sorghum) and legumes (groundnuts, cowpeas). We were able to confirm the role of PhyC gene in pearl millet flowering and identify several other genes that appear to be as much as important, such as FSR12 and HAC1 . HAC1 and two other genes appear to be part of QTLs previously identified and deserve further investigation. At the same time, we were able to highlight a several genes and variants that could contribute to the improvement of pearl millet yield, especially since their impact was demonstrated across flowering cycles.