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.

journal_name

Genetics

journal_title

Genetics

authors

Shiina T,Ota M,Shimizu S,Katsuyama Y,Hashimoto N,Takasu M,Anzai T,Kulski JK,Kikkawa E,Naruse T,Kimura N,Yanagiya K,Watanabe A,Hosomichi K,Kohara S,Iwamoto C,Umehara Y,Meyer A,Wanner V,Sano K,Macquin C,Ikeo K,T

doi

10.1534/genetics.106.057034

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

1555-70

issue

3

eissn

0016-6731

issn

1943-2631

pii

genetics.106.057034

journal_volume

173

pub_type

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