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Abstract

Phylogenetic analyses of DRB intron-1 and intron-2 sequences derived from a variety of primate species suggest that a sequence of duplication events has given rise to the DRB1, B3, B4, B5, and B6 loci. Allelic diversification of DRB1 appears to have preceded the origin of some of these loci. The DRB3 sequences cluster with alleles from the DR51 lineage (DR1 and DR2) and DRB4 is also more closely related to the DR51 than to the DR52 and DR53 lineages. DRB5 and DRB6 sequences diverged before separation of the DRB1 allelic lineages. For DRB1, the divergence of most of the lineages occurred prior to the separation of the hominoids (5-7myr ago), while alleles within a lineage, based on the paucity of intron sequence variation, appear to have diverged recently (within the last 200-300,000 years). Within lineage sequence variation can be detected, however, by analysis of a complex microsatellite in intron-2. We postulate that the structure of this microsatellite has evolved by point mutations from a putative ancestral (GT), (GA),complex dinucleotide repeat. In all contemporary human DRB1 allelic lineages, with the exception of the DR4 lineage, the (GA),repeat is interrupted, often by a G to C transversion, giving rise to a variety of more complex structures. In general, the length of the 3' (GA) repeat correlates with a specific allelic lineage and thus evolves more slowly than the middle (GA) repeat, whose length correlates with a specific allele. The longer 5' (GT) repeat evolves more rapidly than both the middle (GA) repeat and the 3' (GA) repeat, consistent with a higher mutation rate for longer tracts. The length variation in this complex microsatellite repeat was used to trace the origin of new DRB1 alleles, such as the novel DRB 1*08 alleles found in South America.

Keywords

phylogenetic; HLA class II; microsatellite; polymorphism evolution; populations

Published in

Title: Major Histocompatibility Complex : evolution, structure, and function
Publisher: Springer

Conference

6th International Workshop on Major Histocompatibility Complex Evolution

SLU Authors

UKÄ Subject classification

Animal and Dairy Science
Genetics and Genomics

Publication identifier

  • DOI: https://doi.org/10.1007/978-4-431-65868-9_25
  • ISBN: 978-4-431-70276-4
  • eISBN: 978-4-431-65868-9

Permanent link to this page (URI)

https://res.slu.se/id/publ/85996