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

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 SoedaMinoru Kimura, Seiamak Bahram, Hidetoshi Inoko

Research output: Contribution to journalArticlepeer-review

156 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13282-13287
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number23
DOIs
Publication statusPublished - 1999 Nov 9
Externally publishedYes

ASJC Scopus subject areas

  • General

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