Abstract
Genetic recombination has been proposed to have played a major role in generating the extensive polymorphism that distinguishes the genes of the major histocompatibility complex (MHC). The proximal region of the murine H-2 represents a unique segment of DNA encompassing at least four hotspots for meiotic recombination. One of these hotspots lies within the second intron of the class II Eb gene and has been defined at the nucleotide level for a number of simple two-allele crosses. In this report we studied two crosses in which one or both parents in themselves were H2Eb recombinants and three alleles were present within the hotspots of each pair of the parental haplotypes. Nucleotide analysis indicated that the break points in these secondary recombinants, like those in the primary recombinants, were also discrete and clustered within the H2Eb second intron. Thus, in one instance two and in the other instance three alleles were present within the hotspots of these recombinants. These observations strongly suggest that meiotic recombination could be an important mechanism contributing to MHC polymorphism.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bastien, L., Bourgaux, P. 1987. The MT family of mouse DNA is made of short interspersed repeated elements. Gene 57, 81–88.
Begovich, A.B., Thanh, H.V., Jones, P.P. (1990). Characterization of the molecular defects in the mouse Eb f and Eb q genes. Implication for the origin of MHC polymorphism. J. Immunol. 144, 1957–1964.
Bryda, E.C., Depari, J.A., Sant'Angelo, D.B., Murphy, D.B., Passmore, H.C. (1992). Multiple sites of crossing over within the Eb recombinational hotspot in the mouse. Mammalian Genome 2, 123–129.
Folsom, V., Gay, D., Tonegawa, S. (1985). The β1 domain of the mouse Eβ chain is important for restricted antigen presentation to helper T-cell hybridomas. Proc. Natl. Acad. Sci. USA 82, 1678–1682.
Gillies, S.D., Folsom, V., Tonegawa, S. (1984). Cell type-specific enhancer element associated with a mouse MHC gene, Eb. Nature 310, 594–597.
Horton, R.M., Loveland, B.E., Parwani, A., Pease, L.R., Lindahl, K.F. (1991). Characterization of a spontaneous mutant H-2K bm29 indicates that gene conversion in H-2 occurs at a higher frequency than detected by skin grafting. J. Immunol. 147, 3180–3184.
Kobori, J.A., Strauss, E., Minard, K., Hood, L. (1986). Molecular analysis of the hotspot of recombination in the murine major histocompatibility complex. Science 234, 173–179.
Lafuse, W.P., Berg, N., Savarirayan, S., David, C.S. (1986). Mapping of a second recombination hotspot within the I-E region of the mouse H-2 gene complex. J. Exp. Med. 163, 1518–1528.
Mathis, D.J., Benoist, C., Williams II, V.E., Kanter, M., McDevitt, H.O. (1983). Several mechanisms can account for defective Ea gene expression in different mouse haplotypes. Proc. Natl. Acad. Sci. USA 80, 273–277.
Padgett, K.A., Shreffler, D.C., Saha, B.K. (1991a). Molecular mapping of murine I-region recombinants III. Crossing over at two discrete sites within the β1-β2 intron of the Eb gene. J. Immunol. 147, 2764–2770.
Padgett, K.A., Mullersman, J.E., Saha, B.K. (1991b). A novel approach to sequencing DNA amplified by the polymerase chain reaction. BioTechniques 11, 56–58.
Saha, B.K., Raziuddin, Cullen, S.E. (1986). Molecular mapping of murine I-region recombinants II. Crossing over in the Eb gene is restricted to a 4.5 kb stretch of DNA that excludes the β1 exon. J. Immunol. 137, 4004–4009.
Saha, B.K., Shields, J.J., Miller, R.D., Hansen, T.H., Shreffler, D.C. (1993). A highly polymorphic microsatellite in the class II Eb gene allows tracing of MHC evolution. Proc. Natl. Acad. Sci. USA 90, 5312–5316.
She, J.X., Boehme, S.A., Wang, T.W., Bonhomme, F., Wakeland, E.K. (1991). Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination. Proc. Natl. Acad. Sci. USA 88, 453–457.
Shenkar, R., Shen, M., Arnheim, N. (1991). DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse Eb meiotic recombination hotspot. Mol. Cell. Biol. 11, 1813–1819.
Shiroishi, T., Hanzawa, N., Sagai, T., Ishiura, M., Gojobori, T., Steinmetz, M., Moriwaki, K. (1990). Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex. Immunogenetics 31, 79–88.
Shiroishi, T., Sagai, T., Hanzawa, N., Gotoh, H., Moriwaki, K. (1991). Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse. EMBO J. 10, 681–686.
Steinmetz, M., Stephan, D., Fischer-Lindahl, K. (1986). Gene organization and recombinational hotspots in the murine major histocompatibility complex. Cell 44, 895–904.
Sylla, B.S., Allard, D., Roy, G., Bourgaux-Ramoisy, D., Bourgaux, P. (1984). A mouse DNA sequence that mediates integration and excision of polyoma virus DNA. Gene 29, 343–350.
Uematsu, Y., Kiefer, H., Schulze, R., Fischer-Lindahl, K., Steinmetz, M. (1986). Molecular characterization of a meiotic recombinational hotspot enhancing homologous equal crossing-over. EMBO J. 5, 2123–2129.
Wakeland, E.K., Tarnuzzer, R.W., Lu, C.C., Potts, W., McIndoe, R.A., Talbot, W.S., McConnell, T.J. (1987). The evolution of MHC class II genes within the genus Mus. In H-2 Antigens, Genes, Molecules, and Function. C.S. David, ed. New York, N.Y.: Plenum, pp. 139–156.
Zimmer, E.J., Passmore, H.C. (1991). Structural and genetic properties of the Eb recombinational hotspot in the mouse. Immunogenetics 33, 132–140.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Saha, B.K. Recruitment of multiple alleles within the Eb recombinational hotspot in murine MHC. Mammalian Genome 4, 565–570 (1993). https://doi.org/10.1007/BF00361386
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00361386