This Article Full Text Full Text (PDF) Supplemental Reseach Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Daza-Vamenta, R. Articles by Geraghty, D. E. Search for Related Content PubMed PubMed Citation Articles by Daza-Vamenta, R. Articles by Geraghty, D. E. Social Bookmarking                   What's this?

Letter

Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

¹ The Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA ² Institute for Systems Biology, Seattle, Washington 98103, USA

The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque.

³ Corresponding author.
E-MAIL geraghty{at}fhcrc.org; FAX (206) 667-6948.

[Supplemental material is available online at www.genome.org and www.fhcrc.org/labs/geraghty. The sequence data from this study have been submitted to GenBank under accession nos. AC148659–AC148717. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: D. Watkins, D. O'Connor, R. Bontrop, and M.L. Marthas.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. T. Loffredo, A. T. Bean, D. R. Beal, E. J. Leon, G. E. May, S. M. Piaskowski, J. R. Furlott, J. Reed, S. K. Musani, E. G. Rakasz, et al. Patterns of CD8+ Immunodominance May Influence the Ability of Mamu-B*08-Positive Macaques To Naturally Control Simian Immunodeficiency Virus SIVmac239 Replication J. Virol., February 15, 2008; 82(4): 1723 - 1738. [Abstract] [Full Text] [PDF]

				J. P. Giraldo-Vela, R. Rudersdorf, C. Chung, Y. Qi, L. T. Wallace, B. Bimber, G. J. Borchardt, D. L. Fisk, C. E. Glidden, J. T. Loffredo, et al. The Major Histocompatibility Complex Class II Alleles Mamu-DRB1*1003 and -DRB1*0306 Are Enriched in a Cohort of Simian Immunodeficiency Virus-Infected Rhesus Macaque Elite Controllers J. Virol., January 15, 2008; 82(2): 859 - 870. [Abstract] [Full Text] [PDF]

				C. Lundegaard, O. Lund, C. Kesmir, S. Brunak, and M. Nielsen Modeling the adaptive immune system: predictions and simulations Bioinformatics, December 15, 2007; 23(24): 3265 - 3275. [Abstract] [Full Text] [PDF]

				L. Dumas, Y. H. Kim, A. Karimpour-Fard, M. Cox, J. Hopkins, J. R. Pollack, and J. M. Sikela Gene copy number variation spanning 60 million years of human and primate evolution Genome Res., September 1, 2007; 17(9): 1266 - 1277. [Abstract] [Full Text] [PDF]

				N. Yuhki, T. Beck, R. Stephens, B. Neelam, and S. J. O'Brien Comparative Genomic Structure of Human, Dog, and Cat MHC: HLA, DLA, and FLA J. Hered., August 3, 2007; (2007) esm056v1. [Abstract] [Full Text] [PDF]

				A. Averdam, H. Kuhl, M. Sontag, T. Becker, A. L. Hughes, R. Reinhardt, and L. Walter Genomics and Diversity of the Common Marmoset Monkey NK Complex J. Immunol., June 1, 2007; 178(11): 7151 - 7161. [Abstract] [Full Text] [PDF]

				Rhesus Macaque Genome Sequencing and Analysis Cons, R. A. Gibbs, J. Rogers, M. G. Katze, R. Bumgarner, G. M. Weinstock, E. R. Mardis, K. A. Remington, R. L. Strausberg, J. C. Venter, et al. Evolutionary and Biomedical Insights from the Rhesus Macaque Genome Science, April 13, 2007; 316(5822): 222 - 234. [Abstract] [Full Text] [PDF]

				R. W. Wiseman, J. A. Wojcechowskyj, J. M. Greene, A. J. Blasky, T. Gopon, T. Soma, T. C. Friedrich, S. L. O'Connor, and D. H. O'Connor Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius J. Virol., January 1, 2007; 81(1): 349 - 361. [Abstract] [Full Text] [PDF]

				J. A. Wojcechowskyj, L. J. Yant, R. W. Wiseman, S. L. O'Connor, and D. H. O'Connor Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of Mamu-B*17-Containing Haplotypes J. Virol., January 1, 2007; 81(1): 406 - 410. [Abstract] [Full Text] [PDF]

				T. Shiina, M. Ota, S. Shimizu, Y. Katsuyama, N. Hashimoto, M. Takasu, T. Anzai, J. K. Kulski, E. Kikkawa, T. Naruse, et al. Rapid Evolution of Major Histocompatibility Complex Class I Genes in Primates Generates New Disease Alleles in Humans via Hitchhiking Diversity Genetics, July 1, 2006; 173(3): 1555 - 1570. [Abstract] [Full Text] [PDF]

				A. B. McDermott, D. H. O'Connor, S. Fuenger, S. Piaskowski, S. Martin, J. Loffredo, M. Reynolds, J. Reed, J. Furlott, T. Jacoby, et al. Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques J. Virol., December 15, 2005; 79(24): 15556 - 15566. [Abstract] [Full Text] [PDF]

				K. C. Krebs, Z. Jin, R. Rudersdorf, A. L. Hughes, and D. H. O'Connor Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques J. Immunol., October 15, 2005; 175(8): 5230 - 5239. [Abstract] [Full Text] [PDF]

				L. Rowen, E. Williams, G. Glusman, E. Linardopoulou, C. Friedman, M. E. Ahearn, J. Seto, C. Boysen, S. Qin, K. Wang, et al. Interchromosomal Segmental Duplications Explain the Unusual Structure of PRSS3, the Gene for an Inhibitor-Resistant Trypsinogen Mol. Biol. Evol., August 1, 2005; 22(8): 1712 - 1720. [Abstract] [Full Text] [PDF]

				H. D. Hickman-Miller, W. Bardet, A. Gilb, A. D. Luis, K. W. Jackson, D. I. Watkins, and W. H. Hildebrand Rhesus Macaque MHC Class I Molecules Present HLA-B-Like Peptides J. Immunol., July 1, 2005; 175(1): 367 - 375. [Abstract] [Full Text] [PDF]

				N. G. de Groot, C. A. Garcia, E. J. Verschoor, G. G. M. Doxiadis, S. G. E. Marsh, N. Otting, and R. E. Bontrop Reduced MIC Gene Repertoire Variation in West African Chimpanzees as Compared to Humans Mol. Biol. Evol., June 1, 2005; 22(6): 1375 - 1385. [Abstract] [Full Text] [PDF]

				N. T. Pande, C. Powers, K. Ahn, and K. Fruh Rhesus Cytomegalovirus Contains Functional Homologues of US2, US3, US6, and US11 J. Virol., May 1, 2005; 79(9): 5786 - 5798. [Abstract] [Full Text] [PDF]

				N. Otting, C. M. C. Heijmans, R. C. Noort, N. G. de Groot, G. G. M. Doxiadis, J. J. van Rood, D. I. Watkins, and R. E. Bontrop Unparalleled complexity of the MHC class I region in rhesus macaques PNAS, February 1, 2005; 102(5): 1626 - 1631. [Abstract] [Full Text] [PDF]