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MBE Advance Access published online on July 21, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh216
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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Accepted July 16, 2004

Original Articles

Rhesus Macaque Class I Duplicon Structures, Organization and Evolution within the Alpha Block of the Major Histocompatibility Complex

Jerzy K. Kulski 1*, Tatsuya Anzai 2, Takashi Shiina 2, Hidetoshi Inoko 2

1 Centre for Bioinformatics and Biological Computing, School of Information Technology, Murdoch University, Murdoch, Western Australia; Division of Molecular Life Science, Department of Genetic Information, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa-Pref, Japan
2 Division of Molecular Life Science, Department of Genetic Information, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa-Pref, Japan

* To whom correspondence should be addressed. E-mail: jkulski{at}murdoch.edu.au.


  Abstract

The alpha block of the human and chimpanzee Major Histocompatibility Complex (MHC) class I genomic region contains 10-11 duplicated MHC class I genes, including the HLA/Patr-A, -G and -F genes. In comparison, the alpha block of the rhesus macaque (Macaca mulatta, Mamu) has an additional 20 MHC class I genes within this orthologous region. The present study describes the identification and analysis of the duplicated segmental genomic structures (duplicons) and genomic markers within the alpha block of the rhesus macaque and their use to reconstruct the duplication history of the genes within this region. A variety of MHC class I genes, pseudogenes, transposons and retrotransposons, such as Alu and ERV16, were used to categorize the 28 duplicons into four distinct structural categories. The phylogenetic relationship of MHC class I genes, Alu and LTR16B sequences within the duplicons was examined by using the Neighbour Joining (NJ) method. Two single duplicon tandem duplications, two polyduplicon tandem duplications with an accompanying inversion product per duplication, eight polyduplicon tandem duplications steps, 12 deletions and at least two recombinations were reconstructed to explain the highly complex organization and evolution of the 28 duplicons (nine inversions) within the Mamu alpha block. On the basis of the phylogenetic evidence and the reconstructed tandem duplication history of the 28 duplicons, the Mamu/Patr/HLA-F ortholog was the first MHC class I gene to have been fixed without further duplication within the alpha block of primates. Assuming that the rhesus macaque and the chimpanzee/human lineages had started with the same number of MHC class I duplicons at the time of their divergence ~24-31 MYA, then the number of genes within the alpha block have been duplicated at an ~3x greater rate in the rhesus macaque than in either the human or chimpanzee.

Keywords: segmental tandem duplications; MHC genes; retrotransposons; rhesus macaque; comparative genomics.
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