title: Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity.
abstract: 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.
authors.affiliation: Department of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiina
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Sayoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Nami
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Miwa
authors.initials: M
authors.lastname: Takasu
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Anzai
authors.forename: Jerzy K
authors.initials: JK
authors.lastname: Kulski
authors.forename: Eri
authors.initials: E
authors.lastname: Kikkawa
authors.forename: Taeko
authors.initials: T
authors.lastname: Naruse
authors.forename: Natsuki
authors.initials: N
authors.lastname: Kimura
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yanagiya
authors.forename: Atsushi
authors.initials: A
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hosomichi
authors.forename: Sakae
authors.initials: S
authors.lastname: Kohara
authors.forename: Chie
authors.initials: C
authors.lastname: Iwamoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Umehara
authors.forename: Alice
authors.initials: A
authors.lastname: Meyer
authors.forename: Valérie
authors.initials: V
authors.lastname: Wanner
authors.forename: Kazumi
authors.initials: K
authors.lastname: Sano
authors.forename: Cécile
authors.initials: C
authors.lastname: Macquin
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Gojobori
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D019143:Evolution, Molecular; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000276:immunology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology; D011323:Primates / Q000235:genetics* / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA