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A human-specific allelic group of the MHC DRB1 gene in primates

BACKGROUND: Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allel...

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Autores principales: Yasukochi, Yoshiki, Satta, Yoko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072476/
https://www.ncbi.nlm.nih.gov/pubmed/24928070
http://dx.doi.org/10.1186/1880-6805-33-14
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author Yasukochi, Yoshiki
Satta, Yoko
author_facet Yasukochi, Yoshiki
Satta, Yoko
author_sort Yasukochi, Yoshiki
collection PubMed
description BACKGROUND: Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated HLA alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data. RESULTS: Phylogenetic analysis of HLA-DRB1 genes identified two major groups, HLA Groups A and B. Group A formed a monophyletic clade distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven HLA-DRB1 Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa. CONCLUSIONS: HLA Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time.
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spelling pubmed-40724762014-07-01 A human-specific allelic group of the MHC DRB1 gene in primates Yasukochi, Yoshiki Satta, Yoko J Physiol Anthropol Original Article BACKGROUND: Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated HLA alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data. RESULTS: Phylogenetic analysis of HLA-DRB1 genes identified two major groups, HLA Groups A and B. Group A formed a monophyletic clade distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven HLA-DRB1 Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa. CONCLUSIONS: HLA Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time. BioMed Central 2014-06-13 /pmc/articles/PMC4072476/ /pubmed/24928070 http://dx.doi.org/10.1186/1880-6805-33-14 Text en Copyright © 2014 Yasukochi and Satta; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Article
Yasukochi, Yoshiki
Satta, Yoko
A human-specific allelic group of the MHC DRB1 gene in primates
title A human-specific allelic group of the MHC DRB1 gene in primates
title_full A human-specific allelic group of the MHC DRB1 gene in primates
title_fullStr A human-specific allelic group of the MHC DRB1 gene in primates
title_full_unstemmed A human-specific allelic group of the MHC DRB1 gene in primates
title_short A human-specific allelic group of the MHC DRB1 gene in primates
title_sort human-specific allelic group of the mhc drb1 gene in primates
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072476/
https://www.ncbi.nlm.nih.gov/pubmed/24928070
http://dx.doi.org/10.1186/1880-6805-33-14
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