Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

Marcelo A. Fernandez Vina, Jill A. Hollenbach, Kirsten E. Lyke, Marcelo B. Sztein, Martin Maiers, William Klitz, Pedro Cano, Steven Mack, Richard Single, Chaim Brautbar, Shosahna Israel, Eduardo Raimondi, Evelyne Khoriaty, Adlette Inati, Marco Andreani, Manuela Testi, Maria Elisa Moraes, Glenys Thomson, Peter Stastny, Kai Cao

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans.

Original languageEnglish (US)
Pages (from-to)820-829
Number of pages10
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume367
Issue number1590
DOIs
Publication statusPublished - Mar 19 2012

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Keywords

  • Convergent evolution
  • Diversification
  • Histocompatibility
  • HLA
  • Migrations
  • Selection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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