Domínguez-Andrés, JorgeKuijpers, YunusBakker, Olivier B.Jaeger, MartinXu, Cheng-Jianvan der Meer, Jos W.M.Jakobsson, MattiasBertranpetit, Jaume, 1952-Joosten, Leo AbLi, YangNetea, Mihai G2021-11-102021-11-102021Domínguez-Andrés J, Kuijpers Y, Bakker OB, Jaeger M, Xu CJ, Van der Meer JW, Jakobsson M, Bertranpetit J, Joosten LA, Li Y, Netea MG. Evolution of cytokine production capacity in ancient and modern European populations. Elife. 2021;10:e64971. DOI: 10.7554/eLife.649712050-084Xhttp://hdl.handle.net/10230/48941As our ancestors migrated throughout different continents, natural selection increased the presence of alleles advantageous in the new environments. Heritable variations that alter the susceptibility to diseases vary with the historical period, the virulence of the infections, and their geographical spread. In this study we built polygenic scores for heritable traits that influence the genetic adaptation in the production of cytokines and immune-mediated disorders, including infectious, inflammatory, and autoimmune diseases, and applied them to the genomes of several ancient European populations. We observed that the advent of the Neolithic was a turning point for immune-mediated traits in Europeans, favoring those alleles linked with the development of tolerance against intracellular pathogens and promoting inflammatory responses against extracellular microbes. These evolutionary patterns are also associated with an increased presence of traits related to inflammatory and auto-immune diseases.application/pdfeng© 2021, Domínguez-Andrés et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.7554/eLife.64971AdaptationDiseaseEvolutionGeneticsGenomicsHumanImmune systemImmunologyInflammationNeolithicinfo:eu-repo/semantics/openAccess