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

Authors

• Laurent Abi-Rached, Stanford University School of Medicine
• Matthew J. Jobin, Santa Clara University
• Subhash Kulkarni, Stanford University School of Medicine
• Alasdair McWhinnie, Royal Free Hospital, London
• Klara Dalva, Ankara University, Turkey
• Loren Gragert, National Marrow Donor Program, Minneapolis, MN
• Farbod Babrzadeh, Stanford University School of Medicine
• Baback Gharizadeh, Stanford University School of Medicine
• Ma Luo, Public Health Agency of Canada, Winnepeg
• Francis A. Plummer, Public Health Agency of Canada, Winnepeg
• Joshua Kimani, University of Nairobi, Kenya
• Mary Carrington, National Cancer Institute-Frederick, Frederick, MD
• Derek Middleton, Royal Liverpool University Hospital
• Raja Rajalingam, David Geffen School of Medicine at UCLA
• Meral Beksac, Ankara University, Turkey
• Steven G. E. Marsh, Royal Free Hospital, London
• Martin Maiers, National Marrow Donor Program, Minneapolis, MN
• Lisbeth A. Guethlein, Stanford University School of Medicine
• Sofia Tavoularis, Canadian Blood Services, Ottawa
• Ann-Margaret Little, Royal Free Hospital, London
• Richard E. Green, University of California Santa CruzFollow
• Paul J. Norman, Stanford University School of Medicine
• Peter Parham, Stanford University School of Medicine

Date of this Version

2011

Comments

Published in Sciencexpress, http://www.sciencexpress.org 25 August 2011 doi: 10.1126/science.1209202

This article is a U.S. government work, and is not subject to copyright in the United States.

Abstract

Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic 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.

Includes Supporting Material (44 pp.)