Miyada C G, Klofelt C, Reyes A A, McLaughlin-Taylor E, Wallace R B
Proc Natl Acad Sci U S A. 1985 May;82(9):2890-4. doi: 10.1073/pnas.82.9.2890.
The high degree of polymorphism found among the class I genes of the murine major histocompatibility complex (H-2) has led to the postulation that specific genetic mechanisms are responsible for their diversity. These same genetic mechanisms are probably responsible for the high spontaneous mutation frequency seen in H-2 alleles. The bml mutation of the H-2Kb gene has been shown to be 7 base pair changes over a 13 base pair region that result in three amino acid substitutions in the C1 domain of the protein product. The clustering of base-pair changes has suggested that the bm1 mutation resulted from a recombinational event analogous to gene conversion between the H-2Kb gene and a "donor" gene sequence. A 23-base oligonucleotide complementary to the bm1 mutant sequences was synthesized and used to probe genomic DNA restriction digests of the parental H-2b haplotype as well as other H-2 haplotypes. Our results indicate that a potential donor gene sequence is present in the genomes of all of the five mouse strains studied. Of eight tissues that were tested by blot-hybridization analysis, the potential donor gene sequences are transcribed only in the liver. Models for the generation of polymorphism among the H-2 class I genes via subgene rearrangements are proposed.
在小鼠主要组织相容性复合体（H-2）的I类基因中发现的高度多态性，促使人们推测特定的遗传机制是其多样性的原因。这些相同的遗传机制可能也是H-2等位基因中高自发突变频率的原因。已证明H-2Kb基因的bm1突变是在一个13个碱基对的区域内发生了7个碱基对的变化，导致蛋白质产物的C1结构域中有三个氨基酸替换。碱基对变化的聚集表明，bm1突变是由类似于H-2Kb基因与“供体”基因序列之间基因转换的重组事件引起的。合成了一个与bm1突变序列互补的23个碱基的寡核苷酸，并用于探测亲本H-2b单倍型以及其他H-2单倍型的基因组DNA限制性消化产物。我们的结果表明，在所研究的所有五个小鼠品系的基因组中都存在一个潜在的供体基因序列。在通过印迹杂交分析测试的八个组织中，潜在的供体基因序列仅在肝脏中被转录。本文提出了通过亚基因重排产生H-2 I类基因多态性的模型。
