, Volume 59, Issue 4, pp 261–271 | Cite as

Full-length sequence analysis of the HLA-DRB1 locus suggests a recent origin of alleles

  • Jenny von Salomé
  • Ulf Gyllensten
  • Tomas F. BergströmEmail author
Original Paper


The HLA region harbors some of the most polymorphic loci in the human genome. Among them is the class II locus HLA-DRB1, with more than 400 known alleles. The age of the polymorphism and the rate at which new alleles are generated at HLA loci has caused much controversy over the years. Previous studies have mostly been restricted to the 270 base pairs that constitute the second exon and represent the most variable part of the gene. Here, we investigate the evolutionary history of the HLA-DRB1 locus on the basis of an analysis of 15 genomic full-length alleles (10–15 kb). In addition, the variation in 49 complete coding sequences and 322 exon 2 sequences were analyzed. When excluding exon 2 from the analysis, the diversity at the synonymous sites was found to be similar to the intron diversity. The overall diversity in noncoding region was also similar to the genome average. The DRB1*03 lineage has been found in human, chimpanzee, bonobo, gorilla, and orangutan. An ancestral “proto HLA-DRB1*03 lineage” appeared to have diverged in the last 5 million years into the human-specific lineages *08, *11, *13, and *14. With exception to exon 2, both the coding- and the noncoding diversity suggests a recent origin (<1 million years ago) for most of the alleles at the HLA-DRB1 locus. Sites encoding for amino acids involved in antigen binding [antigen recognizing sites (ARS)] appear to have a more ancient origin. Taken together, the recent origin of most alleles, the high diversity between allelic lineages, and the ancient origin of sequence motifs in exon 2, is consistent with a relatively rapid generation of novel alleles by gene conversion like events.


HLA MHC DRB1 Intron Evolution Polymorphisms 



This work was supported by grants from the Graduate Research School in Genomics and Bioinformatics, the Swedish Natural Science Research Council, the Erik Philip-Sörensen foundation, the Beijer foundation, the Marcus Borgström Foundation, and the Magnus Bergvall Foundation.

Supplementary material

251_2007_196_MOESM1_ESM.doc (36 kb)
Table S1a Sequencing primers, HLA-DRB1 fragment 1 (DOC 36 kb)
251_2007_196_MOESM2_ESM.doc (37 kb)
Table S1b Sequencing primers, HLA-DRB1 fragment 2 (DOC 37 kb)
251_2007_196_MOESM3_ESM.doc (30 kb)
Table S2 HLA-DRB1 alleles in dataset A, B, and C (DOC 31 kb)
251_2007_196_MOESM4_ESM.doc (26 kb)
Table S3 Intron diversity within lineages, dataset A (DOC 26 kb)


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jenny von Salomé
    • 1
  • Ulf Gyllensten
    • 1
  • Tomas F. Bergström
    • 1
    • 2
    Email author
  1. 1.Department of Genetics and Pathology, Rudbeck LaboratoryUppsala UniversityUppsalaSweden
  2. 2.Linnaeus Center for BioinformaticsUppsala UniversityUppsalaSweden

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