Evidence for polygenic adaptation to pathogens in the human genome.

Details

Serval ID
serval:BIB_5B46808B83ED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evidence for polygenic adaptation to pathogens in the human genome.
Journal
Molecular Biology and Evolution
Author(s)
Daub J.T., Hofer T., Cutivet E., Dupanloup I., Quintana-Murci L., Robinson-Rechavi M., Excoffier L.
ISSN
1537-1719 (Electronic)
ISSN-L
0737-4038
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
30
Number
7
Pages
1544-1558
Language
english
Abstract
Most approaches aiming at finding genes involved in adaptive events have focused on the detection of outlier loci, which resulted in the discovery of individually "significant" genes with strong effects. However, a collection of small effect mutations could have a large effect on a given biological pathway that includes many genes, and such a polygenic mode of adaptation has not been systematically investigated in humans. We propose here to evidence polygenic selection by detecting signals of adaptation at the pathway or gene set level instead of analyzing single independent genes. Using a gene-set enrichment test to identify genome-wide signals of adaptation among human populations, we find that most pathways globally enriched for signals of positive selection are either directly or indirectly involved in immune response. We also find evidence for long-distance genotypic linkage disequilibrium, suggesting functional epistatic interactions between members of the same pathway. Our results show that past interactions with pathogens have elicited widespread and coordinated genomic responses, and suggest that adaptation to pathogens can be considered as a primary example of polygenic selection.
Keywords
human evolution, pathway analysis, adaptation, polygenic selection, epistasis
Pubmed
Web of science
Create date
22/04/2013 9:55
Last modification date
20/08/2019 15:14
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