HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional dif...

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Autores principales:	Stéphane Buhler, Alicia Sanchez-Mazas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0bf484f212c44afdb164b92198678554
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spelling	oai:doaj.org-article:0bf484f212c44afdb164b921986785542021-11-18T06:59:21ZHLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.1932-620310.1371/journal.pone.0014643https://doaj.org/article/0bf484f212c44afdb164b921986785542011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21408106/?tool=EBIhttps://doaj.org/toc/1932-6203Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution.Stéphane BuhlerAlicia Sanchez-MazasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e14643 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stéphane Buhler Alicia Sanchez-Mazas HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.
description	Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC) genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model). However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used to explore the genetic history of human populations, and that their analysis allows a more thorough investigation of human MHC molecular evolution.
format	article
author	Stéphane Buhler Alicia Sanchez-Mazas
author_facet	Stéphane Buhler Alicia Sanchez-Mazas
author_sort	Stéphane Buhler
title	HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.
title_short	HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.
title_full	HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.
title_fullStr	HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.
title_full_unstemmed	HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.
title_sort	hla dna sequence variation among human populations: molecular signatures of demographic and selective events.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/0bf484f212c44afdb164b92198678554
work_keys_str_mv	AT stephanebuhler hladnasequencevariationamonghumanpopulationsmolecularsignaturesofdemographicandselectiveevents AT aliciasanchezmazas hladnasequencevariationamonghumanpopulationsmolecularsignaturesofdemographicandselectiveevents
_version_	1718424083582943232

HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

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