Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region.
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.
Shiina
T
T
Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Tamiya
G
G
Oka
A
A
Takishima
N
N
Yamagata
T
T
Kikkawa
E
E
Iwata
K
K
Tomizawa
M
M
Okuaki
N
N
Kuwano
Y
Y
Watanabe
K
K
Fukuzumi
Y
Y
Itakura
S
S
Sugawara
C
C
Ono
A
A
Yamazaki
M
M
Tashiro
H
H
Ando
A
A
Ikemura
T
T
Soeda
E
E
Kimura
M
M
Bahram
S
S
Inoko
H
H
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