The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules

<p>Abstract</p> <p>Background</p> <p>Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.</p> <p>Results</p> <p>By comparing sequences of eight functional homologues of HLA-E from primates and r...

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Main Authors: Rouillon Virginie, Joly Etienne
Format: Article
Language:English
Published: BMC 2006-01-01
Series:Biology Direct
Online Access:http://www.biology-direct.com/content/1/1/2
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author Rouillon Virginie
Joly Etienne
author_facet Rouillon Virginie
Joly Etienne
author_sort Rouillon Virginie
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.</p> <p>Results</p> <p>By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the α3 domain, but our results suggest that homogenisation also concerns certain residues of the α1–α2 codomain that lie outside the antigen recognition site.</p> <p>Conclusion</p> <p>A model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'être of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation.</p> <p>Reviewers</p> <p>This article was reviewed by Stephan Beck, Lutz Walter and Pierre Pontarotti.</p>
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spelling doaj.art-6d13cb6ffbbe43208ca00b0ec1fae7402022-12-21T20:38:45ZengBMCBiology Direct1745-61502006-01-0111210.1186/1745-6150-1-2The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I moleculesRouillon VirginieJoly Etienne<p>Abstract</p> <p>Background</p> <p>Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate.</p> <p>Results</p> <p>By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the α3 domain, but our results suggest that homogenisation also concerns certain residues of the α1–α2 codomain that lie outside the antigen recognition site.</p> <p>Conclusion</p> <p>A model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'être of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation.</p> <p>Reviewers</p> <p>This article was reviewed by Stephan Beck, Lutz Walter and Pierre Pontarotti.</p>http://www.biology-direct.com/content/1/1/2
spellingShingle Rouillon Virginie
Joly Etienne
The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
Biology Direct
title The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
title_full The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
title_fullStr The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
title_full_unstemmed The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
title_short The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules
title_sort orthology of hla e and h2 qa1 is hidden by their concerted evolution with other mhc class i molecules
url http://www.biology-direct.com/content/1/1/2
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