PMID- 26459025 OWN - NLM STAT- MEDLINE DCOM- 20160223 LR - 20190108 IS - 1432-1211 (Electronic) IS - 0093-7711 (Print) IS - 0093-7711 (Linking) VI - 67 IP - 11-12 DP - 2015 Nov TI - HLA supertype variation across populations: new insights into the role of natural selection in the evolution of HLA-A and HLA-B polymorphisms. PG - 651-63 LID - 10.1007/s00251-015-0875-9 [doi] AB - Supertypes are groups of human leukocyte antigen (HLA) alleles which bind overlapping sets of peptides due to sharing specific residues at the anchor positions-the B and F pockets-of the peptide-binding region (PBR). HLA alleles within the same supertype are expected to be functionally similar, while those from different supertypes are expected to be functionally distinct, presenting different sets of peptides. In this study, we applied the supertype classification to the HLA-A and HLA-B data of 55 worldwide populations in order to investigate the effect of natural selection on supertype rather than allelic variation at these loci. We compared the nucleotide diversity of the B and F pockets with that of the other PBR regions through a resampling procedure and compared the patterns of within-population heterozygosity (He) and between-population differentiation (G ST) observed when using the supertype definition to those estimated when using randomized groups of alleles. At HLA-A, low levels of variation are observed at B and F pockets and randomized He and G ST do not differ from the observed data. By contrast, HLA-B concentrates most of the differences between supertypes, the B pocket showing a particularly high level of variation. Moreover, at HLA-B, the reassignment of alleles into random groups does not reproduce the patterns of population differentiation observed with supertypes. We thus conclude that differently from HLA-A, for which supertype and allelic variation show similar patterns of nucleotide diversity within and between populations, HLA-B has likely evolved through specific adaptations of its B pocket to local pathogens. FAU - Dos Santos Francisco, Rodrigo AU - Dos Santos Francisco R AD - Department of Genetics and Evolutionary Biology, University of Sao Paulo, Sao Paulo, Brazil. biorodrigo2001@yahoo.com.br. AD - Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution-Anthropology Unit, University of Geneva, Geneva, Switzerland. biorodrigo2001@yahoo.com.br. AD - Hospital Israelita Albert Einstein, Sao Paulo, Brazil. biorodrigo2001@yahoo.com.br. FAU - Buhler, Stephane AU - Buhler S AD - Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution-Anthropology Unit, University of Geneva, Geneva, Switzerland. AD - Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Genetic and Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland. FAU - Nunes, Jose Manuel AU - Nunes JM AD - Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution-Anthropology Unit, University of Geneva, Geneva, Switzerland. AD - Institute of Genetics and Genomics in Geneva (IGE3), Geneva, Switzerland. FAU - Bitarello, Barbara Domingues AU - Bitarello BD AD - Department of Genetics and Evolutionary Biology, University of Sao Paulo, Sao Paulo, Brazil. FAU - Franca, Gustavo Starvaggi AU - Franca GS AD - Department of Biochemistry, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brazil. AD - Molecular Oncology Center, Sirio-Libanes Hospital, Sao Paulo, Brazil. FAU - Meyer, Diogo AU - Meyer D AD - Department of Genetics and Evolutionary Biology, University of Sao Paulo, Sao Paulo, Brazil. diogo@ib.usp.br. FAU - Sanchez-Mazas, Alicia AU - Sanchez-Mazas A AD - Laboratory of Anthropology, Genetics and Peopling History, Department of Genetics and Evolution-Anthropology Unit, University of Geneva, Geneva, Switzerland. alicia.sanchez-mazas@unige.ch. AD - Institute of Genetics and Genomics in Geneva (IGE3), Geneva, Switzerland. alicia.sanchez-mazas@unige.ch. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151012 PL - United States TA - Immunogenetics JT - Immunogenetics JID - 0420404 RN - 0 (HLA-A Antigens) RN - 0 (HLA-B Antigens) RN - 0 (Immunodominant Epitopes) SB - IM MH - *Biological Evolution MH - Computer Simulation MH - Databases, Factual MH - *Genetics, Population MH - HLA-A Antigens/classification/*genetics/immunology MH - HLA-B Antigens/classification/*genetics/immunology MH - Histocompatibility Testing MH - Humans MH - Immunodominant Epitopes MH - International Agencies MH - Polymorphism, Genetic/*genetics MH - Selection, Genetic/*genetics PMC - PMC4636516 OTO - NOTNLM OT - Adaptation OT - HLA OT - Human populations OT - Natural selection OT - Pathogens OT - Supertypes EDAT- 2015/10/16 06:00 MHDA- 2016/02/26 06:00 PMCR- 2015/10/12 CRDT- 2015/10/14 06:00 PHST- 2015/06/28 00:00 [received] PHST- 2015/09/29 00:00 [accepted] PHST- 2015/10/14 06:00 [entrez] PHST- 2015/10/16 06:00 [pubmed] PHST- 2016/02/26 06:00 [medline] PHST- 2015/10/12 00:00 [pmc-release] AID - 10.1007/s00251-015-0875-9 [pii] AID - 875 [pii] AID - 10.1007/s00251-015-0875-9 [doi] PST - ppublish SO - Immunogenetics. 2015 Nov;67(11-12):651-63. doi: 10.1007/s00251-015-0875-9. Epub 2015 Oct 12.