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Sequence divergence of B2m alleles of wild Mus musculus and Mus spretus implies positive selection

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Abstract

Mouse β2-microglobulin (β2m) is polymorphic. Sequences of five allelic wild mouse B2m genes have been determined from the large exons of genomic DNA using the polymerase chain reaction. Relative to the standard B2m a allele, the products of four alleles of Mus musculus origin (w2, w3, w4, and w5), differ by only one or two amino acids. w5 has a single nucleotide change, Asp85 → Val, and is identical to the c allele. w2 differs at Arg81 → Thr and w4 at His34 → Gln, and they share the Asp85 → Val change with B2m c and B2m w5.w5 and c cells are lysed by S19.8, a monoclonal antibody specific for β2mb (Ala85), in a complement-mediated cytotoxicity assay, whereas w4 cells are not. Thus, distant changes appear to introduce subtle conformational effects on β2m structure. Five independent isolates of Mus spretus (w1) differ the most from B2m a, with 12 amino acid changes and only one silent substitution. Replacements predicted from the nucleotide sequence occur in loops of the molecule facing away from the class I heavy chain and not in regions where β2m associates with class 1 α3 domains. Concordantly, the w1 – 5 allelic forms of β2m associate well with H-2 heavy chains. The many amino acid changes in the spretus sequence and the paucity of silent substitutions suggest that B2m has been subject to positive selection.

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  1. Howard Hughes Medican Institute, Graduate Immunology Program and the Department of Microbiology and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, 75235-9050, Dallas, TX, USA

    Evan Hermel & Kirstein Fischer Lindahl

  2. Transplantation Biology, Clinical Research Center, Watford Road, HA1 3UJ, Harrow, Middlesex, England

    Peter J. Robinson

  3. Laboratory of Molecular Biology, Department of Pathology, University of Florida, 32610, Gainesville, FL, USA

    Jin-Xiong She

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  1. Evan Hermel
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The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M84362-M84367 and L04992-L04994.

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Hermel, E., Robinson, P.J., She, JX. et al. Sequence divergence of B2m alleles of wild Mus musculus and Mus spretus implies positive selection. Immunogenetics 38, 106–116 (1993). https://doi.org/10.1007/BF00190898

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