TY - JOUR
T1 - Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity
AU - Shiina, Takashi
AU - Ota, Masao
AU - Shimizu, Sayoko
AU - Katsuyama, Yoshihiko
AU - Hashimoto, Nami
AU - Takasu, Miwa
AU - Anzai, Tatsuya
AU - Kulski, Jerzy K.
AU - Kikkawa, Eri
AU - Naruse, Taeko
AU - Kimura, Natsuki
AU - Yanagiya, Kazuyo
AU - Watanabe, Atsushi
AU - Hosomichi, Kazuyoshi
AU - Kohara, Sakae
AU - Iwamoto, Chie
AU - Umehara, Yumi
AU - Meyer, Alice
AU - Wanner, Valérie
AU - Sano, Kazumi
AU - Macquin, Cécile
AU - Ikeo, Kazuho
AU - Tokunaga, Katsushi
AU - Gojobori, Takashi
AU - Inoko, Hidetoshi
AU - Bahram, Seiamak
PY - 2006
Y1 - 2006
N2 - 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 nonhuman 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 haplotype-specific (hs) and hypervariable (hv) (which could not be traced to a single species or haplotype) SNVs 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 overrepresentation of a fraction of these hvSNV (hv1SNV) along with hsSNV, as compared to those that appear to have been maintained throughout primate evolution (trans-species diversity; tsSNV; included within hv2SNV) tends to establish that the majority of the MHC polymorphism is de novo (species specific). This is most likely reminiscent of the fact that these hsSNV and hv1SNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.
AB - 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 nonhuman 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 haplotype-specific (hs) and hypervariable (hv) (which could not be traced to a single species or haplotype) SNVs 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 overrepresentation of a fraction of these hvSNV (hv1SNV) along with hsSNV, as compared to those that appear to have been maintained throughout primate evolution (trans-species diversity; tsSNV; included within hv2SNV) tends to establish that the majority of the MHC polymorphism is de novo (species specific). This is most likely reminiscent of the fact that these hsSNV and hv1SNV have been selected in adaptation to the constantly evolving microbial antigenic repertoire.
UR - http://www.scopus.com/inward/record.url?scp=33746443445&partnerID=8YFLogxK
U2 - 10.1534/genetics.106.057034
DO - 10.1534/genetics.106.057034
M3 - Article
C2 - 16702430
AN - SCOPUS:33746443445
SN - 0016-6731
VL - 173
SP - 1555
EP - 1570
JO - Genetics
JF - Genetics
IS - 3
ER -
