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Published online on June 10, 2003, 10.1073/pnas.1230533100

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Genetics
Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Tatsuya Anzai {dagger}, Takashi Shiina {dagger}, Natsuki Kimura {dagger}, Kazuyo Yanagiya {dagger}, Sakae Kohara {dagger}, Atsuko Shigenari {dagger}, Tetsushi Yamagata {dagger}, Jerzy K. Kulski {dagger}{ddagger}, Taeko K. Naruse {dagger}, Yoshifumi Fujimori §, Yasuhito Fukuzumi §, Masaaki Yamazaki §, Hiroyuki Tashiro §, Chie Iwamoto ¶, Yumi Umehara ¶, Tadashi Imanishi ||, Alice Meyer {dagger}{dagger}, Kazuho Ikeo ¶, Takashi Gojobori ¶, Seiamak Bahram {dagger}{dagger}, and Hidetoshi Inoko {dagger}{ddagger}{ddagger}

{dagger}Department of Genetic Information, Division of Molecular Life Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan; {ddagger}Centre for Bioinformatics and Biological Computing, School of Information Technology, Murdoch University, Murdoch WA 6150, Australia; §Bioscience Research Laboratory, Fujiya Company, Limited, 228 Soya, Hadano, Kanagawa 257-0031, Japan; National Institute of Genetics Center for Information Biology and DDBJ, 1111 Yata, Mishima, Shizuoka 411-8540, Japan; ||Japan Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, TIME24 Building 10F, 2-45 Aomi, Koto-ku, Tokyo 135-0064, Japan; and {dagger}{dagger}Institut National de la Santé et de la Recherche Médicale-Contrat de Recherche Stratégique, Laboratoire d'Immunogénétique Moléculaire Humaine, Centre de Recherche d'Immunologie et d'Hématologie, 4 Rue Kirschleger, 67085 Strasbourg, France

Edited by Masatoshi Nei, Pennsylvania State University, University Park, PA, and approved April 23, 2003 (received for review January 29, 2003)

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ({approx}6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.

{ddagger}{ddagger}To whom correspondence should be addressed.

E-mail: hinoko{at}is.icc.u-tokai.ac.jp.

www.pnas.org/cgi/doi/10.1073/pnas.1230533100
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