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International audience With the advent of next-generation sequencing, paleogenetics has ă considerably expanded over the past few years and notably encompassed ă the characterization of the genomes of archaic humans who lived more ă than 30,000 years ago. These paleogenetics investigations have revealed ă that admixture between modern and archaic humans occurred, with ă Neanderthals having contributed to 1.5% to 2.1% of modern Eurasian ă genomes, and Denisovans to 3% to 6% of modern Melanesian genomes and ă to approximately 0.2% of modern Asian genomes. Although these ă contributions are modest, they played a major role in shaping immune ă gene families, such as the HLA class I genes, for which the archaic ă alleles now represent more than 50% of the alleles in Europe and Asia. ă Such a high frequency is consistent with these archaic HLA class I ă variants having been positively selected because of their protective ă effect against contagious and devastating epidemics, such as those due ă to the plague agent Yersinia pestis or to Mycobacterium tuberculosis, ă which is responsible for deadly tuberculosis. While the exact nature of ă the infectious agents that contributed to the selection of the archaic ă variants is unknown, we are entering an exciting period in which ă paleogenetics and paleomicrobiology data can be integrated to generate a ă clearer picture of how the immune system of modern populations was ă shaped and the role admixture and epidemics have played in such ă evolutions.