A highly polymorphic microsatellite in the class II Eb gene allows tracing of major histocompatibility complex evolution in mouse.
A highly polymorphic microsatellite in the class II Eb gene allows tracing of major histocompatibility complex evolution in mouse.
复制标题
II 类 Eb 基因中的高度多态性微卫星可以追踪小鼠主要组织相容性复合体的进化。
DOI：
10.1073/pnas.90.11.5312
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发表时间：
1993
影响因子：
11.1
通讯作者：
Shreffler,DC
中科院分区：
文献类型：
--
作者：
Saha,BK;Shields,JJ;Miller,RD;Hansen,TH;Shreffler,DC
主要组织相容性复合体（MHC）基因的一个标志是其异常高水平的多态性。MHC分子上的多态性残基决定了它们与哪些肽配体结合并呈递给效应T淋巴细胞。虽然负责MHC多态性的遗传机制已被划定，其多样化的时间表和途径仍不清楚。为了追踪MHC的进化，我们在小鼠Class II Eb基因第二内含子的3'端发现了一个高度多态的微卫星，它含有两个四核苷酸单元TGGA和GGCA的串联重复序列（TRs）。根据长度和序列变异，在55个近交系小鼠中确定了11个TR等位基因，包括MHC重组单倍型和来自不同亚种小鼠的单倍型。在这个广泛的采样，一个惊人的一致性之间观察到血清学鉴定的II类蛋白质和相关的TR等位基因。对携带相同MHC单倍型的几个菌株以及携带重组MHC单倍型的菌株的检查表明TR等位基因非常稳定。这些观察结果表明，TR多态性早于小鼠的各种亚种的分离。在序列差异的基础上，构建了一个系谱树来描述不同TR等位基因的进化。最后，证据表明，这种微卫星多态性产生的DNA复制过程中的滑动链错配。
A hallmark of major histocompatibility complex (MHC) genes is their extraordinarily high level of polymorphism. Polymorphic residues on MHC molecules determine which peptide ligands they bind and present to effector T lymphocytes. Although the genetic mechanisms responsible for MHC polymorphism have been delineated, the timetable and the pathway of their diversification remain unclear. To trace MHC evolution, we have characterized a highly polymorphic microsatellite containing tandem repeats (TRs) of two tetranucleotide units, TGGA and GGCA, located at the 3' end of the second intron in the class II Eb gene of mouse. On the basis of length as well as sequence variations, 11 TR alleles were defined in 55 inbred mouse strains, which included MHC recombinant haplotypes and haplotypes derived from different subspecies of mouse. In this extensive sampling, a striking concordance was observed between the serologically identified class II proteins and the associated TR alleles. Examination of several strains carrying the same MHC haplotypes as well as strains carrying recombinant MHC haplotypes indicates that TR alleles are extremely stable. These observations suggest that TR polymorphism predates the separation of various subspecies of mouse. On the basis of sequence divergence, a genealogical tree has been constructed to depict evolution of the different TR alleles. Finally, evidence is presented that suggests this microsatellite polymorphism is generated by slipped-strand mispairing during DNA replication.