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.
Highlights
Human history has been shaped by infectious diseases
Not all the stimuli induce the production of all cytokines; so the selection of the cytokine-stimulus pairs was performed for those pairs for which cytokine production was measurable (Li et al, 2016; Ruschen et al, 1992; Schirmer et al, 2016; Ter Horst et al, 2016; van de Veerdonk et al, 2009)
We correlated cytokine production with genetic variant data to obtain cytokine quantitative trait loci (QTLs), which were employed to compute and compare the polygenic risk score (PRS) of the genomes of 827 individuals from different human historical eras, which were downloaded from version 37.2 of the compiled dataset containing unimputed published ancient genotypes and 250 modern Europeans randomly selected from the European 1000G cohort
Summary
Human history has been shaped by infectious diseases. Human genes, especially host defense genes, have been constantly influenced by the pathogens encountered (Fumagalli and Sironi, 2014; Karlsson et al, 2014; Quintana-Murci and Clark, 2013). Genetics and Genomics Immunology and Inflammation survival to diseases with high morbidity and mortality will be naturally selected in people before reproductive age (Karlsson et al, 2014). These selection signatures vary with historical period, virulence of the pathogen, and the geographical spread. Within the HFGP project, the 500FG study generated a large database of immunological, phenotypic, and multi-omics data from a cohort of 534 individuals of Western-European ancestry, which has been used to integrate the impact of genetic and environmental factors on cytokine production and immune parameters. We subsequently deciphered the factors that influence inter-individual variations in the immune responses against different stimuli (Bakker et al, 2018; Li et al, 2016; Schirmer et al, 2016; Ter Horst et al, 2016)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
