The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans

• Published in: Science (American Association for the Advancement of Science) Vol. 334; no. 6052; pp. 89 - 94
• Main Authors: Abi-Rached, Laurent, Jobin, Matthew J., Kulkarni, Subhash, McWhinnie, Alasdair, Dalva, Klara, Gragert, Loren, Babrzadeh, Farbod, Gharizadeh, Baback, Luo, Ma, Plummer, Francis A., Kimani, Joshua, Carrington, Mary, Middleton, Derek, Rajalingam, Raja, Beksac, Meral, Marsh, Steven G. E., Maiers, Martin, Guethlein, Lisbeth A., Tavoularis, Sofia, Little, Ann-Margaret, Green, Richard E., Norman, Paul J., Parham, Peter
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 07.10.2011; The American Association for the Advancement of Science
• Subjects: Adaptation, Biological; Admixtures; Africans; Alleles; Animals; Antigens; Asian People - genetics; Biological and medical sciences; Black People - genetics; Classical genetics, quantitative genetics, hybrids; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Genes, MHC Class I; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Genomics; genotyping; Haplotypes; HLA A antigens; HLA antigens; HLA B antigens; HLA C antigens; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-A Antigens - metabolism; HLA-B Antigens - genetics; HLA-B Antigens - immunology; HLA-B Antigens - metabolism; HLA-C Antigens - genetics; HLA-C Antigens - immunology; Hominidae - genetics; Hominidae - immunology; Human; Human populations; Humans; Hybridization, Genetic; Immune system; introgression; Killer Cells, Natural - immunology; Leukocytes; Ligands; Linkage Disequilibrium; Molecular Sequence Data; Native Hawaiian or Pacific Islander - genetics; natural killer cells; Polymorphism; Racial Groups - genetics; receptors; Receptors, KIR - immunology; Receptors, KIR - metabolism; Selection, Genetic; West Asia; White People - genetics; West Asia; Human; Molecular evolution; Histocompatibility system; Genetics; Genome; Introgression; Class I histocompatibility antigen
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1209202

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.