The shaping of modern human immune systems by multiregional admixture with archaic humans |
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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 |
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Institution: | Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. |
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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. |
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