Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations | Zendy

Hélène Quach | Zendy; Maxime Rotival | Zendy; Julien Pothlichet | Zendy; YongHwee Eddie Loh | Zendy; Michael Dannemann | Zendy; Nora Zidane | Zendy; Guillaume Laval | Zendy; Étienne Patin | Zendy; Christine Harmant | Zendy; Marie Lopez | Zendy; Matthieu Deschamps | Zendy; Nadia Naffakh | Zendy; Darragh Duffy | Zendy; Anja Coen | Zendy; Geert LerouxRoels | Zendy; Frédéric Clement | Zendy; Anne Boland | Zendy; JeanFrançois Deleuze | Zendy; Janet Kelso | Zendy; Matthew L. Albert | Zendy; Lluís QuintanaMurci | Zendy

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Genetic Adaptation and Neandertal Admixture Shaped the Immune System of Human Populations

Author(s) -

Hélène Quach,

Maxime Rotival,

Julien Pothlichet,

YongHwee Eddie Loh,

Michael Dannemann,

Nora Zidane,

Guillaume Laval,

Étienne Patin,

Christine Harmant,

Marie Lopez,

Matthieu Deschamps,

Nadia Naffakh,

Darragh Duffy,

Anja Coen,

Geert LerouxRoels,

Frédéric Clement,

Anne Boland,

JeanFrançois Deleuze,

Janet Kelso,

Matthew L. Albert,

Lluís QuintanaMurci

Publication year - 2016

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2016.09.024

Subject(s) - biology , expression quantitative trait loci , immune system , genetics , population , tlr7 , gene , quantitative trait locus , adaptation (eye) , evolutionary biology , genome wide association study , toll like receptor , innate immune system , single nucleotide polymorphism , genotype , demography , neuroscience , sociology

Humans differ in the outcome that follows exposure to life-threatening pathogens, yet the extent of population differences in immune responses and their genetic and evolutionary determinants remain undefined. Here, we characterized, using RNA sequencing, the transcriptional response of primary monocytes from Africans and Europeans to bacterial and viral stimuli-ligands activating Toll-like receptor pathways (TLR1/2, TLR4, and TLR7/8) and influenza virus-and mapped expression quantitative trait loci (eQTLs). We identify numerous cis-eQTLs that contribute to the marked differences in immune responses detected within and between populations and a strong trans-eQTL hotspot at TLR1 that decreases expression of pro-inflammatory genes in Europeans only. We find that immune-responsive regulatory variants are enriched in population-specific signals of natural selection and show that admixture with Neandertals introduced regulatory variants into European genomes, affecting preferentially responses to viral challenges. Together, our study uncovers evolutionarily important determinants of differences in host immune responsiveness between human populations.

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