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

Laurent Abi‐Rached(Stanford University), Matthew J. Jobin(Santa Clara University), Subhash Kulkarni(Stanford University), Alasdair McWhinnie(Anthony Nolan), Klara Dalva(Ankara University), Loren Gragert(National Marrow Donor Program), Farbod Babrzadeh(Stanford University), Baback Gharizadeh(Stanford University), Ma Luo(Public Health Agency of Canada), Francis A. Plummer(Public Health Agency of Canada), Joshua Kimani(University of Nairobi), Mary Carrington(Ragon Institute of MGH, MIT and Harvard), Derek Middleton(University of Liverpool), Raja Rajalingam(University of California, Los Angeles), Meral Beksaç(Ankara University), Steven G. E. Marsh(Anthony Nolan), Martin Maiers(National Marrow Donor Program), Lisbeth A. Guethlein(Stanford University), Sofia Tavoularis(Canadian Blood Services), Ann‐Margaret Little(Anthony Nolan), Richard E. Green(University of California, Santa Cruz), Paul J. Norman(Stanford University), Peter Parham(Stanford University)
Science
August 25, 2011
10.1126/science.1209202
Cited by 559Open Access
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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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