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Evolutionary relationship between human major histocompatibility complex HLA-DR haplotypes

A C Svensson1, N Setterblad, U Pihlgren

  • 1Uppsala Genetic Center, Department of Cell Research, Swedish University of Agricultural Sciences, Box 7055, S-750 07 Uppsala, Sweden.

Immunogenetics
|January 1, 1996
PubMed
Summary
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This study reveals endogenous retroviral elements in human major histocompatibility complex (MHC) DR haplotypes. Phylogenetic analysis suggests DR1 and DR51 haplotypes share a close evolutionary history, possibly involving gene deletion.

Area of Science:

  • Immunogenetics
  • Molecular Evolution
  • Human Genetics

Background:

  • Human major histocompatibility complex (MHC) includes HLA-DR haplotypes organized into five groups.
  • Haplotypes are identified by DRB1 locus serological specificity and DRB gene composition.

Purpose of the Study:

  • To determine nucleotide sequences of introns 4 and 5 for DRB genes in DR1 and DR51 haplotypes.
  • To investigate evolutionary relationships and potential gene deletion events between these haplotypes.

Main Methods:

  • Nucleotide sequencing of specific introns (4 and 5) from DRB1, DRB6, and DRB5 genes.
  • Phylogenetic analysis to infer evolutionary relationships.

Main Results:

  • Identical endogenous retroviral long terminal repeat (ERV9 LTR) elements were found at conserved positions in intron 5 of DRB1 genes from both DR1 and DR51 haplotypes.

Related Experiment Videos

  • Phylogenetic analyses indicated a close evolutionary relationship between DR1 and DR51 haplotypes.
  • The DRB5 gene, present in DR51, may have been lost in the DR1 haplotype via gene deletion.

    • Conclusions:

    • A model for human DR haplotype evolution, involving gene duplication and contraction, is proposed.
    • Endogenous retroviral elements may play a role in MHC haplotype evolution.
    • Gene deletion events likely contributed to the diversification of human DR haplotypes.