Evolution of cytokine production capacity in ancient and modern European populations

Author:

Domínguez-Andrés Jorge12ORCID,Kuijpers Yunus34ORCID,Bakker Olivier B5,Jaeger Martin12,Xu Cheng-Jian134ORCID,Van der Meer Jos WM1,Jakobsson Mattias67,Bertranpetit Jaume8,Joosten Leo AB12ORCID,Li Yang1234ORCID,Netea Mihai G129ORCID

Affiliation:

1. Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

2. Radboud Institute for Molecular Life Sciences (RIMLS), RadboudUniversity Medical Center, Nijmegen, Netherlands

3. Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany

4. TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany

5. Department of Genetics, University Medical Centre Groningen, Nijmegen, Netherlands

6. Human Evolution, Department of Organismal Biology, Uppsala University, Uppsala, Sweden

7. Centre for Anthropological Research, Department of Anthropology and Development Studies, University of Johannesburg, Auckland Park, South Africa

8. Institut de Biologia Evolutiva (UPF-CSIC), Universitat Pompeu Fabra, Barcelona, Spain

9. Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany

Abstract

As 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.

Funder

European Commission

ZonMw

Netherlands Organisation for Scientific Research

Radboud University Medical Center

MINECO

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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