Abstract
We have determined the molecular maps of theH-2D andQa regions of thet-complex haplotypest l2 andt w5 by chromosomal walking. Analysis with class I probes and other probes unique to theH-2D:Qa subregion indicates that the class I gene organization oft 12 is:D1-D2-Q1-Q2-Q3-Qx-Q4-Q5-Q10, while that oft w5 is:D1-D2-Q1-Q2-Q4-Q5-Q10. Thus, the absence of theQ6-Q9 genes suggested previously int-haplotypes was confirmed. A comparison of the molecular maps of thet 12 andt w5 chromosomes revealed an extremely mosaic pattern of diversity: The regions betweenD1 andD2, and betweenQ4 andQ10, are very similar in both chromosomes. However, theirQ1 toQ3 regions are strikingly different. Further comparisons of wild-type chromosomes and additionalt-haplotypes by molecular mapping and genomic Southern blot hybridization with probes to theQ1-Q3 region showed a high level of polymorphism among both wild-type chromosomes and amongt-haplotypes. The characteristics of the polymorphisms suggest that recombination may play an important role in generating this genetic diversity. Furthermore, recombination between wild-type andt-haplotype chromosomes may be involved.
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Artzt, K., Shin, H.-S., and Bennett, D.: Gene mapping within theT/t complex of the mouse. II. Anomalous position of theH-2 complex int-haplotypes.Cell 28: 471, 1982.
Artzt, K., Shin, H.-S., Bennett, D., and Dimeo-Talento, A.: Analysis of major histocompatibility complex haplotypes oft-chromosomes reveals that the majority of diversity is generated by recombination.J Exp Med 162: 93, 1985.
Bennett, D.: TheT-locus of the mouse.Cell 6: 441, 1975.
Bennett, D., Alton, A.K., and Artzt, K.: Genetic analysis of transmission ratio distortion byt-haplotypes in the mouse.Genet Res 41: 29, 1983.
Figueroa, F., Günther, E., and Klein, J.: MHC polymorphism predating speciation.Nature 335: 265, 1988.
Hammer, M.F., Schimenti, J., and Silver, L.M.: Evolution of mouse chromosome 17 and the origin of inversions associated witht-haplotypes.Proc Natl Acad Sci USA 86: 3261, 1989.
Herrmann, B.G., Bucán, M., Mains, P.E., Frischauf, A.-M., Silver, L.M. and Lehrach, H.: Genetic analysis of the proximal portion of the mouset-complex: Evidence for a second inversion withint-haplotypes.Cell 44: 469, 1986.
Hood, L., Steinmetz, M., and Mallissen, B.: Genes of the major histocompatibility complex of the mouse.Ann Rev Immunol 1: 529, 1983.
Hughes, A.L., and Nei, M.: Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection.Nature 335: 167, 1988.
Klein, J.Natural History of the Major Histocompatibility Complex, John Wiley and Sons, New York, 1986.
Lawlor, D.A., Ward, F.E., Ennis, P.D., Jackson, A.P., and Parham, P.: HLA-A and B polymorphism predate the divergence of humans and chimpanzees.Nature 335: 268, 1988.
Lawlor, D.A., Zemmour, J., Ennis, P.D., and Parham, P.: Evolution of class I MHC genes and proteins: From natural selection to thymic selection.Ann Rev Immunol 8: 23, 1990.
Lyon, M.F.: Transmission ratio distortion in mouset-haplotypes is due to multiple distorter genes acting on a responder locus.Cell 37: 621, 1984.
McConnell, T.J., Talbot, W.S., McIndoe, R.A., and Wakeland, E.K.: The origin of MHC class II gene polymorphism within the genus.Mus. Nature 332: 651, 1988.
Nathenson, S.G., Geliebter, J., Pfaffenbach, G.M., and Zeff, R.A.: Murine major histocompatibility complex class I mutants: Molecular analysis and structure-function implications.Ann Rev Immunol 4: 471, 1986.
Nei, M., and Li, W.-H.: Mathematical model for studying genetic variation in terms of restriction endonucleases.Proc Natl Acad Sci USA 76: 5269, 1979.
Nižetić, D., Figueroa, F. and Klein, J.: Evolutionary relationships between thet andH-2 haplotypes in the house mouse.Immunogenetics 19: 311, 1984.
O'Neill, A.E., Reid, K., Garberi, J.C., Karl, M., and Flaherty, L.: Extensive deletions in theQ region of the mouse major histocompatibility complex.Immunogenetics 24: 368, 1986.
Rackwitz, H.R., Zehetner, G., Frischauf, A.-M., and Lehrach, H.: Analysis of cosmids using linearization of phage lambda terminase.Gene 40: 259, 1985.
Röhme, D., Fox, H., Herrmann, B., Frischauf, A.-M., Edström, J.-E., Mains, P., Silver, L.M., and Lehrach, H.: Molecular clones of the mouset-complex derived from microdissected metaphase chromosomes.Cell 36: 783, 1984.
Rogers, J.H., Lyon, M.F., and Willison, K.R.: The arrangement ofH-2 class I genes in mouset-haplotypes.J Immunogenetics 12: 151, 1985.
Shin, H.-S., Stavnezer, J., Artzt, K., and Bennett, D.: Genetic structure and origin oft-haplotypes of mice, analyzed withH-2 cDNA probes.Cell 29: 969, 1982.
Shin, H.-S., Flaherty, L., Artzt, K., Bennett, D., and Ravetch, J.: Inversion in theH-2 complex oft-haplotypes in mice.Nature 306: 380, 1983.
Silver, L.M.: Genomic analysis of theH-2 complex region associated with mouset-haplotypes.Cell 29: 961, 1982.
Silver, L.M.: Mouset-haplotypes.Ann Rev Genet 19: 179, 1985.
Silver, L.M., Hammer, M.F., Fox, H., Garrels, J., Bucan, M., Herrmann B., Frischauf, A.-M., Lehrach, H., Winking, H., Figueroa, F., and Klein, J.: Molecular evidence for the rapid propagation of mouset-haplotypes from a single, recent, ancestral chromosome.Mol Biol Evol 4: 473, 1987.
Steinmetz, M., Frelinger, J.G., Fisher, D., Hunkapiller, T., Pereira, D., Weissman, S.M., Uehara, H., Nathenson, S.G., and Hood, L.: Three cDNA clones encoding transplantation antigens: Homology to immunoglobin genes.Cell 24: 125, 1981.
Steinmetz, M., Winoto, A., Minard, K., and Hood, L.: Clusters of genes encoding mouse transplantation antigens.Cell 28: 489, 1982.
Steinmetz, M., Mallisen, M., Hood, L., Ört, A., Maki, R.A., Dastoornikoo, G.R., Stephan, D., Gibb, E., and Remaniuk, R.: Tracts of high or low sequence divergence in the mouse major histocompatibility complex.EMBO J 3: 2995, 1984.
Uehara, H., Abe, K., Park, C.-H.T., Shin, H.-S., Bennett, D., and Artzt, K.: The molecular organization of theH-2K region of twot-haplotypes: Implications for the evolution of genetic diversity.EMBO J 6: 83, 1987.
Watts, S., Davis, A.C., Gaut, B., Wheeler, C., Hill, L., and Goodenow, R.S.: Organization and structure of theQa genes of the major histocompatibility complex of the C3H mouse: Implications forQa function and class I evolution.EMBO J 8: 1749, 1989.
Weiss, E.H., Golden, L., Fahrner, K., Mellor, A.L., Devlin, J.J., Bullman, H., Tiddens, H., Bud, M., and Flavell, R.A.: Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse.Nature 310: 650, 1984.
Willison, K.R., Dudley, K., and Potter, J.: Molecular cloning and sequence analysis of a haploid expressed gene encodingt-complexpolypeptide-1.Cell 44: 727, 1986.
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Uehara, H., Abe, K., Flaherty, L. et al. Molecular organization of theD-Qa region oft-haplotypes suggests that recombination is an important mechanism for generating genetic diversity of the major histocompatibility complex. Mammalian Genome 1, 92–99 (1991). https://doi.org/10.1007/BF02443784
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DOI: https://doi.org/10.1007/BF02443784