The shaping of modern human immune systems by multiregional admixture with archaic humans

Laurent Abi-Rached; Matthew J. Jobin; Subhash Kulkarni; Alasdair McWhinnie; Klara Dalva; Loren Gragert; Farbod Babrzadeh; Baback Gharizadeh; Ma Luo; Francis A. Plummer; Joshua Kimani; Mary Carrington; Derek Middleton; Raja Rajalingam; Meral Beksac; Steven G.E. Marsh; Martin Maiers; Lisbeth A. Guethlein; Sofia Tavoularis; Ann Margaret Little; Richard E. Green; Paul J. Norman; Peter Parham

doi:10.1126/science.1209202

The shaping of modern human immune systems by multiregional admixture with archaic humans

Laurent Abi-Rached, Matthew J. Jobin, Subhash Kulkarni, Alasdair McWhinnie, Klara Dalva, Loren Gragert, Farbod Babrzadeh, Baback Gharizadeh, Ma Luo, Francis A. Plummer, Joshua Kimani, Mary Carrington, Derek Middleton, Raja Rajalingam, Meral Beksac, Steven G.E. Marsh, Martin Maiers, Lisbeth A. Guethlein, Sofia Tavoularis, Ann Margaret LittleRichard E. Green, Paul J. Norman, Peter Parham

Research output: Contribution to journal › Article › peer-review

296 Scopus citations

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.

Original language	English (US)
Pages (from-to)	89-94
Number of pages	6
Journal	Science
Volume	334
Issue number	6052
DOIs	https://doi.org/10.1126/science.1209202
State	Published - Oct 7 2011
Externally published	Yes

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Abi-Rached, L., Jobin, M. J., Kulkarni, S., McWhinnie, A., Dalva, K., Gragert, L., Babrzadeh, F., Gharizadeh, B., Luo, M., Plummer, F. A., Kimani, J., Carrington, M., Middleton, D., Rajalingam, R., Beksac, M., Marsh, S. G. E., Maiers, M., Guethlein, L. A., Tavoularis, S., ... Parham, P. (2011). The shaping of modern human immune systems by multiregional admixture with archaic humans. Science, 334(6052), 89-94. https://doi.org/10.1126/science.1209202

Abi-Rached, L, Jobin, MJ, Kulkarni, S, McWhinnie, A, Dalva, K, Gragert, L, Babrzadeh, F, Gharizadeh, B, Luo, M, Plummer, FA, Kimani, J, Carrington, M, Middleton, D, Rajalingam, R, Beksac, M, Marsh, SGE, Maiers, M, Guethlein, LA, Tavoularis, S, Little, AM, Green, RE, Norman, PJ & Parham, P 2011, 'The shaping of modern human immune systems by multiregional admixture with archaic humans', Science, vol. 334, no. 6052, pp. 89-94. https://doi.org/10.1126/science.1209202

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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.",

author = "Laurent Abi-Rached and Jobin, {Matthew J.} and Subhash Kulkarni and Alasdair McWhinnie and Klara Dalva and Loren Gragert and Farbod Babrzadeh and Baback Gharizadeh and Ma Luo and Plummer, {Francis A.} and Joshua Kimani and Mary Carrington and Derek Middleton and Raja Rajalingam and Meral Beksac and Marsh, {Steven G.E.} and Martin Maiers and Guethlein, {Lisbeth A.} and Sofia Tavoularis and Little, {Ann Margaret} and Green, {Richard E.} and Norman, {Paul J.} and Peter Parham",

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AU - Dalva, Klara

AU - Gragert, Loren

AU - Babrzadeh, Farbod

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AU - Plummer, Francis A.

AU - Kimani, Joshua

AU - Carrington, Mary

AU - Middleton, Derek

AU - Rajalingam, Raja

AU - Beksac, Meral

AU - Marsh, Steven G.E.

AU - Maiers, Martin

AU - Guethlein, Lisbeth A.

AU - Tavoularis, Sofia

AU - Little, Ann Margaret

AU - Green, Richard E.

AU - Norman, Paul J.

AU - Parham, Peter

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AB - 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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The shaping of modern human immune systems by multiregional admixture with archaic humans

Abstract

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