The Relative Contributions of Gene Conversion-Like Substitutions and Unique Mutations Toward Polymorphism Among MHC Class I Genes
One of the most intriguing characteristics of the murine major histocompatibility complex (MHC) is the high degree of polymorphism associated with the class I and class II loci mapping in the K, D, and I regions. This polymorphism has two components. The first is the large number of alleles identified in the wild (Klein and Figueroa, 1981). None of these alleles is present in the population at high frequencies and the total number of alleles is estimated at over 100 (Goetze et al., 1980). The second component of this extraordinary polymorphism is the extensive structural diversity distinguishing alleles. Whereas allelic variants at other loci typically differ by a single or a few amino acids (Gates et al., 1981; Perlmutter et al., 1984; Kimura and Nerbert, 1986), MHC alleles tend to differ by 5 to 10 percent of their amino acids. The amino terminal 273 amino acids, which compose the extracellular portion of four class I alleles of the H-2K locus, are shown in Figure 1. The sequences are divided into three 91 amino acid segments representing the exon structure of the K structural gene. Comparison of these sequences reveals the high degree of structural diversity which is most prominent in the first two segments encompassing amino acids 1 through 182, but also discernible in the more conserved regions of the glycoprotein represented here by amino acids 183 through 273. Diversity in the amino terminal 182 amino acids is known to influence function (see Duran and Pease, 1986 for review). Sequence variation within this segment of the H-2K glycoprotein may be influenced by natural selection. Conversely, no functional differences have been associated with diversity in the remainder of the glycoprotein. Many of these substitutions may be selectively neutral.
KeywordsMajor Histocompatibility Complex Major Histocompatibility Complex Class None None Major Histocompatibility Complex Allele Transplantation Antigen
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