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doi:10.1534/genetics.106.057034
A more recent version of this article appeared on July 1, 2006.
REGULAR RESEARCH PAPERS |
Rapid Evolution of MHC Class I Genes in Primates Generates New Disease Alleles in Man Via Hitchhiking Diversity
Takashi Shiina 1, Masao Ota 2, Sayoko Shimizu 1, Yoshihiko Katsuyama 3, Nami Hashimoto 1, Miwa Takasu 4, Tatsuya Anzai 1, Jerzy K. Kulski 5, Eri Kikkawa 1, Taeko Naruse 1, Natsuki Kimura 1, Kazuyo Yanagiya 1, Atsushi Watanabe 1, Kazuyoshi Hosomichi 1, Sakae Kohara 6, Chie Iwamoto 7, Yumi Umehara 7, Alice Meyer 8, Valerie Wanner 8, Kazumi Sano 1, Cecile Macquin 8, Kazuho Ikeo 7, Katsushi Tokunaga 4, Takashi Gojobori 7, Hidetoshi Inoko 1 and Seiamak Bahram 8*
1 Tokai University School of Medicine
2 Shinshu University School of Medicine
3 Shinshu University Hospital
4 University of Tokyo
5 Murdoch University
6 Shin Nippon Biomedical Laboratories (SNBL) Ltd.
7 National Institute of Genetics
8 Faculte de Médecine
* To whom correspondence should be addressed. E-mail: siamak{at}hemato-ulp.u-strasbg.fr.
Submitted on February 20, 2006
Revised on March 22, 2006
Accepted on 2 May 2006
A plausible explanation for many MHC-linked diseases is lacking. Sequencing of the MHC class I region (coding units or full contigs) in several human and non-human primate haplotypes allowed an analysis of Single Nucleotide Variations (SNV) across this entire segment. This diversity was not evenly distributed. It was rather concentrated within two gene-rich clusters. These were each centered, but importantly not limited to, the antigen-presenting HLA-A and HLA-B/-C loci. Rapid evolution of MHC-I alleles, as evidenced by an unusually high number of cross-species "hypervariable SNV" (hvSNV) within the classical MHC-I, seems to have not only hitchhiked alleles within nearby genes, but also hitchhiked deleterious mutations in these same unrelated loci. The over-representation of these hvSNV with respect to those which appear to have been maintained throughout primate evolution (trans-species diversity) tends to establish that the majority of MHC polymorphism is de novo (species-specific). This is most likely reminiscent of the fact that these hvSNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.
Key Words: HLA, Immunogenetics, MHC, Major Histocompatibility Complex
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