Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination.
Amplification of major histocompatibility complex class II gene diversity by intraexonic recombination.
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DOI：
10.1073/pnas.88.2.453
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发表时间：
1991-01
影响因子：
11.1
通讯作者：
Jin-Xiong She;Stefen Boehme;Tie Wang;F. Bonhomme;Edward K. Wakeland
中科院分区：
文献类型：
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作者：
Jin-Xiong She;Stefen Boehme;Tie Wang;F. Bonhomme;Edward K. Wakeland
突变和重组过程中的外显子编码的抗原结合位点在小鼠主要组织相容性复合体II类基因抗体的多样化的作用进行了评估等位基因核苷酸序列的系统发育分析。应用聚合酶链反应（PCR）技术对12个小鼠种或亚种和2个家鼠种的Ab基因外显子2的46个等位基因进行了测序。可靠的等位基因系谱不能确定系统发育分析，由于广泛的同源性的数据集。这种同源性是由等位基因之间的多态性通过重组过程的改组引起的，表明由Ab编码的抗原结合位点中的多态性是由两种过程的组合产生的。首先，点突变的积累产生了高度不同的多态性序列基序在五个区域的抗体外显子2，每个编码的结合位点的一部分。这些基序中的一些在啮齿动物中作为多态性一直存在，因为在小鼠和大鼠分化之前（超过1000万年前）。介导抗体多样化的第二个过程涉及通过重复的外显子内重组将这些多态性序列基序改组成许多等位基因组合。位点特异性超重组机制不参与外显子内的这一过程。我们假设，这些机制不断产生新的抗体等位基因具有高度不同的结合位点，从等位基因具有有利的抗原结合特性的选择性保持某种形式的平衡选择。
The roles of mutational and recombinational processes in the diversification of the exon encoding the antigen binding site in the murine major histocompatibility complex class II gene Ab were assessed by phylogenetic analysis of allelic nucleotide sequences. A total of 46 alleles of Ab exon 2 from 12 Mus species or subspecies and 2 Rattus species were sequenced after amplification by the polymerase chain reaction. Reliable allelic genealogies could not be determined by phylogenetic analyses, due to extensive homoplasy in the data set. This homoplasy results from the shuffling of polymorphisms between alleles by recombinational processes, indicating that polymorphisms in the antigen binding site encoded by Ab are generated by a combination of two processes. First, the accumulation of point mutations has produced highly divergent polymorphic sequence motifs in five regions of Ab exon 2, each encoding a portion of the binding site. Some of these motifs have persisted as polymorphisms in rodents since before the divergence of mouse and rat (greater than 10 million years ago). The second process mediating Ab diversification involves the shuffling of these polymorphic sequence motifs into numerous allelic combinations by repeated intraexonic recombination. Site-specific hyperrecombinational mechanisms are not involved in this process within the exon. We postulate that these mechanisms continuously generate new Ab alleles with highly divergent binding sites from which alleles with advantageous antigen-binding properties are selectively maintained by some form of balancing selection.