title: Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region.
abstract: The intensely studied MHC has become the paradigm for understanding the architectural evolution of vertebrate multigene families. The 4-Mb human MHC (also known as the HLA complex) encodes genes critically involved in the immune response, graft rejection, and disease susceptibility. Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F. A total of 127 genes or potentially coding sequences were recognized within the analyzed sequence, establishing a high gene density of one per every 14.1 kb. The identification of 758 microsatellite provides tools for high-resolution mapping of HLA class I-associated disease genes. Most importantly, we establish that the repeated duplication and subsequent diversification of a minimal building block, MIC-HCGIX-3.8-1-P5-HCGIV-HLA class I-HCGII, engendered the present-day MHC. That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA/B genes provides experimental evidence for evolution by "birth and death," which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.
authors.affiliation: Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shiina
authors.forename: G
authors.initials: G
authors.lastname: Tamiya
authors.forename: A
authors.initials: A
authors.lastname: Oka
authors.forename: N
authors.initials: N
authors.lastname: Takishima
authors.forename: T
authors.initials: T
authors.lastname: Yamagata
authors.forename: E
authors.initials: E
authors.lastname: Kikkawa
authors.forename: K
authors.initials: K
authors.lastname: Iwata
authors.forename: M
authors.initials: M
authors.lastname: Tomizawa
authors.forename: N
authors.initials: N
authors.lastname: Okuaki
authors.forename: Y
authors.initials: Y
authors.lastname: Kuwano
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuzumi
authors.forename: S
authors.initials: S
authors.lastname: Itakura
authors.forename: C
authors.initials: C
authors.lastname: Sugawara
authors.forename: A
authors.initials: A
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Yamazaki
authors.forename: H
authors.initials: H
authors.lastname: Tashiro
authors.forename: A
authors.initials: A
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Ikemura
authors.forename: E
authors.initials: E
authors.lastname: Soeda
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Bahram
authors.forename: H
authors.initials: H
authors.lastname: Inoko
mesh_terms: D020029:Base Pairing; D005075:Biological Evolution; D005805:Genes, MHC Class I; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid