Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region

• DOI: 10.1073/pnas.96.23.13282
• Publication Date: 2002-07-26T14:38:21Z
• Authors: Takashi Shiina; Gen Tamiya; Akira Oka; Nobusada Takishima; Tetsushi Yamagata; Eri Kikkawa; Kyoko Iwata; Maiko Tomizawa; Noriko Okuaki; Yuko Kuwano; Koji Watanabe; Yasuhito Fukuzumi; Shoko Itakura; Chiyo Sugawara; Ayako Ono; Masaaki Yamazaki; Hiroyuki Tashiro; Asako Ando; Toshimichi Ikemura; Eiichi Soeda; Minoru Kimura; Seiamak Bahram; Hidetoshi Inoko
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Molecular Sequence Data; Genes, MHC Class I; Humans; Base Pairing; Biological Evolution; Microsatellite Repeats; Repetitive Sequences, Nucleic Acid

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 betweenMICBandHLA-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 nonessentialHLA-FandMICEgenes have acted as progenitors to today’s immune-competentHLA-ABCandMICA/Bgenes provides experimental evidence for evolution by “birth and death,” which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.