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Shiina, T. et al.

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.[1]

References

Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region. Shiina, T., Tamiya, G., Oka, A., Takishima, N., Yamagata, T., Kikkawa, E., Iwata, K., Tomizawa, M., Okuaki, N., Kuwano, Y., Watanabe, K., Fukuzumi, Y., Itakura, S., Sugawara, C., Ono, A., Yamazaki, M., Tashiro, H., Ando, A., Ikemura, T., Soeda, E., Kimura, M., Bahram, S., Inoko, H. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]

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