McCormack W T, Thompson C B
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0650.
Genes Dev. 1990 Apr;4(4):548-58. doi: 10.1101/gad.4.4.548.
Chicken immunoglobulin variable region diversity is generated during B-cell development in the bursa of Fabricius by intrachromosomal gene conversion, resulting in the replacement of sequence blocks within the unique rearranged VL1 and VH1 genes with homologous sequences derived from V region pseudogene segments (psi V). In this report, the nucleotide sequences of 217 gene conversion events in 52 random IgL clones were analyzed to characterize the molecular mechanism of gene conversion. The frequency of psi VL usage as gene conversion donors is shown to depend on the proximity of the psi VL segment to VL1, extent of homology with VL1, and relative orientation of the psi VL segments. Gene conversion events are not observed in the 5' region of homology between psi VL segments and VL1, but are distributed throughout the remainder of the VL1 exon. The 5' ends of individual gene conversion events always begin in regions of homology between the donor psi VL and recipient VL1 gene, whereas the 3' ends can occur in regions of nonhomology and often have nucleotide insertions or deletions. These results suggest a 5' to 3' polarity in the gene conversion mechanism. The implications of our data are discussed in relation to current molecular models of gene conversion.
鸡免疫球蛋白可变区多样性是在法氏囊中B细胞发育过程中通过染色体内基因转换产生的，导致独特重排的VL1和VH1基因内的序列块被源自V区假基因片段（psi V）的同源序列所取代。在本报告中，分析了52个随机IgL克隆中217个基因转换事件的核苷酸序列，以表征基因转换的分子机制。结果表明，psi VL作为基因转换供体的使用频率取决于psi VL片段与VL1的接近程度、与VL1的同源程度以及psi VL片段的相对方向。在psi VL片段与VL1之间的同源性5'区域未观察到基因转换事件，但分布在VL1外显子的其余部分。单个基因转换事件的5'端总是始于供体psi VL与受体VL1基因之间的同源区域，而3'端可出现在非同源区域，且经常有核苷酸插入或缺失。这些结果表明基因转换机制中存在5'到3'的极性。我们的数据的意义将结合当前的基因转换分子模型进行讨论。
