HLA-DRA promoter polymorphism and diversity generation within the immune system

Multiple major histocompatibility complex (MHC) alleles exist at most class I and II loci. Polymorphism of MHC polypeptides may reflect either different levels of selective pressure operating on each molecule or different mutation rates at different loci. To gain further insight into this issue, we...

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Bibliographic Details
Published in:Human genetics 1997-06, Vol.99 (6), p.801-805
Main Authors: SCHWIEBERT, L. M, HUGHES, A, MONOS, D. S, ONO, S. J
Format: Article
Language:English
Subjects:
Alleles
Biological and medical sciences
Cell Line
Classical genetics, quantitative genetics, hybrids
Epstein-Barr virus
Evolution, Molecular
Fundamental and applied biological sciences. Psychology
Genetic Linkage
Genetic Variation
Genetics of eukaryotes. Biological and molecular evolution
HLA-DQ Antigens - genetics
HLA-DQ beta-Chains
HLA-DR alpha-Chains
HLA-DR Antigens - genetics
Human
Humans
Polymorphism, Genetic
Promoter Regions, Genetic
Sequence Alignment
Sequence Analysis, DNA
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Summary:Multiple major histocompatibility complex (MHC) alleles exist at most class I and II loci. Polymorphism of MHC polypeptides may reflect either different levels of selective pressure operating on each molecule or different mutation rates at different loci. To gain further insight into this issue, we sequenced the non-coding promoter region of the HLA-DRA gene from several Epstein-Barr virus-transformed B cell lines and compared the extent of polymorphism found in this region with the known polymorphism of the HLA-DQB promoter. Our results indicate that the HLA-DRA promoter displays a low level of polymorphism while the promoter of HLA-DQB exhibits a nucleotide substitution rate fivefold greater than that of DRA. Moreover, through phylogenetic analysis, the HLA-DRA promoter was found to have diverged much less than the associated alleles of HLA-DRB1 and -DQA1. Taken together, these results suggest that the HLA-DRA promoter is highly conserved and may be under a stronger functional constraint than the promoter regions of other MHC class II genes.
ISSN:0340-6717
1432-1203
DOI:10.1007/s004390050452