title: Worldwide HLA-E nucleotide and haplotype variability reveals a conserved gene for coding and 3' untranslated regions.
abstract: The human leukocyte antigen-E (HLA-E) locus is a human major histocompatibility complex (MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific natural killer (NK) and T cell receptors (TCRs). It is considered one of the most conserved genes of the human MHC; however, this low nucleotide variability seems to be a consequence of the scarce number of studies focusing on this subject. In this manuscript we assessed the nucleotide variability at the HLA-E coding and 3' untranslated regions (3'UTRs) in Brazil and in the populations from the 1000Genomes Consortium. Twenty-eight variable sites arranged into 33 haplotypes were detected and most of these haplotypes (98.2%) are encoding one of the two HLA-E molecules found worldwide, E*01:01 and E*01:03. Moreover, three worldwide spread haplotypes, associated with the coding alleles E*01:01:01, E*01:03:01 and E*01:03:02, account for 85% of all HLA-E haplotypes, suggesting that they arose early before human speciation. In addition, the low nucleotide diversity found for the HLA-E coding and 3'UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system.
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
authors.forename: L P
authors.initials: LP
authors.lastname: Felício
authors.forename: I O P
authors.initials: IO
authors.lastname: Porto
authors.forename: C T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.forename: L C
authors.initials: LC
authors.lastname: Veiga-Castelli
authors.forename: K E
authors.initials: KE
authors.lastname: Santos
authors.forename: R P
authors.initials: RP
authors.lastname: Vianello-Brondani
authors.forename: A
authors.initials: A
authors.lastname: Sabbagh
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
authors.forename: E C
authors.initials: EC
authors.lastname: Castelli
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D001483:Base Sequence; D001938:Brazil; D017124:Conserved Sequence; D049810:Genetic Speciation; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000145:classification* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010802:Phylogeny; D011110:Polymorphism, Genetic; D000097625:HLA-E Antigens
chemical_list: D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens
keywords: haplotypes; human leukocyte antigen-E; lineages; natural selection; variability