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

2015

Article référencé dans le Web of Science WOS:000348358100008

Gineau Laure, Luisi P., Castelli E. C., Milet Jacqueline, Courtin David, Cagnin N., Patillon B., Laayouni H., Moreau P., Donadi E. A., Garcia André, Sabbagh A.

Genes and Immunity, 2015, 16 (1), p. 57-70 ISSN 1466-4879

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.

Sciences fondamentales / Techniques d'analyse et de recherche [020] ; Santé : généralités [050]

SENEGAL ; BENIN ; CONGO

Fonds IRD [F B010063915]

fdi:010063915