Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

被引：0
作者：
L Gineau
P Luisi
E C Castelli
J Milet
D Courtin
N Cagnin
B Patillon
H Laayouni
P Moreau
E A Donadi
A Garcia
A Sabbagh
机构：
[1] Institute of Research for Development,Departamento de Patologia
[2] Mixed Research Unit 216 MERIT,Division of Clinical Immunology
[3] Faculté de Pharmacie,undefined
[4] Université Paris Descartes,undefined
[5] Sorbonne Paris Cité,undefined
[6] Institute of Evolutionary Biology,undefined
[7] CEXS-UPF-PRBB,undefined
[8] Faculdade de Medicina,undefined
[9] UNESP—Univ Estatual Paulista,undefined
[10] IRD,undefined
[11] UMR 216,undefined
[12] Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l’Enfance (CERPAGE),undefined
[13] Faculté des Sciences de la Santé,undefined
[14] School of Medicine of Ribeirão Preto,undefined
[15] University of São Paulo,undefined
[16] Université Paris Sud,undefined
[17] Commissariat à l'Energie Atomique et aux Energies Alternatives,undefined
[18] institut des Maladies Emergentes et des Thérapies Innovantes,undefined
[19] Service de Recherches en Hémato-Immunologie,undefined
[20] Hôpital Saint-Louis,undefined
[21] Université Paris Diderot,undefined
[22] Sorbonne Paris Cité,undefined
[23] UMR_E5,undefined
[24] Institut Universitaire d'Hématologie,undefined
[25] Hôpital Saint-Louis,undefined
来源：
Genes & Immunity | 2015年 / 16卷
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摘要：
Human leukocyte antigen-G (HLA-G) has well-recognized immunosuppressive properties modulating the activity of many immune system cells, and polymorphisms observed at the HLA-G 5′ upstream regulatory region (5′URR) may influence gene transcriptional regulation. In this study, we characterized the sequence variation and haplotype structure of the HLA-G 5′URR in worldwide populations to investigate the evolutionary history of the HLA-G promoter and shed some light into the mechanisms that may underlie HLA-G expression control. A 1.4-kb region, encompassing the known HLA-G regulatory elements, was sequenced in three African populations from Senegal, Benin and Congo, and data were combined with those available in the literature, resulting in a total of 1411 individuals from 21 worldwide populations. High levels of nucleotide and haplotype diversities, excess of intermediate-frequency variants and reduced population differentiation were observed at this locus when compared with the background genomic variation. These features support a strong molecular signature of balancing selection at HLA-G 5′URR, probably as a result of the competing needs to maintain both a maternal–fetal immune tolerance and an efficient host immune response to invading pathogens during human evolution. An extended analysis of a 300-kb region surrounding HLA-G revealed that this region is not involved in a hitchhiking effect and may be the direct target of selection.
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页码：57 / 70
页数：13
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