title: The shaping of modern human immune systems by multiregional admixture with archaic humans.
abstract: Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abi-Rached
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Jobin
authors.forename: Subhash
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Alasdair
authors.initials: A
authors.lastname: McWhinnie
authors.forename: Klara
authors.initials: K
authors.lastname: Dalva
authors.forename: Loren
authors.initials: L
authors.lastname: Gragert
authors.forename: Farbod
authors.initials: F
authors.lastname: Babrzadeh
authors.forename: Baback
authors.initials: B
authors.lastname: Gharizadeh
authors.forename: Ma
authors.initials: M
authors.lastname: Luo
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
authors.forename: Joshua
authors.initials: J
authors.lastname: Kimani
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Derek
authors.initials: D
authors.lastname: Middleton
authors.forename: Raja
authors.initials: R
authors.lastname: Rajalingam
authors.forename: Meral
authors.initials: M
authors.lastname: Beksac
authors.forename: Steven G E
authors.initials: SG
authors.lastname: Marsh
authors.forename: Martin
authors.initials: M
authors.lastname: Maiers
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: Sofia
authors.initials: S
authors.lastname: Tavoularis
authors.forename: Ann-Margaret
authors.initials: AM
authors.lastname: Little
authors.forename: Richard E
authors.initials: RE
authors.lastname: Green
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Norman
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
mesh_terms: D000220:Adaptation, Biological; D000483:Alleles; D000818:Animals; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D019143:Evolution, Molecular; D005805:Genes, MHC Class I; D014644:Genetic Variation; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D015186:Hominidae / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D006824:Hybridization, Genetic; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics; D044469:Racial Groups / Q000235:genetics*; D054340:Receptors, KIR / Q000276:immunology / Q000378:metabolism; D012641:Selection, Genetic; D044465:White People / Q000235:genetics
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; C088197:HLA-B73 antigen; D015236:HLA-C Antigens; D008024:Ligands; D054340:Receptors, KIR