Diaz M, Flajnik M F
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida, USA.
Immunol Rev. 1998 Apr;162:13-24. doi: 10.1111/j.1600-065x.1998.tb01425.x.
Examples of somatic hypermutation of antigen receptor genes can be seen in most lineages of vertebrates, including the cartilaginous fish. Analysis of the phylogenetic data reveals that two distinctive features of the mechanism are shared by most species studied: the mutation hot spot sequence AGY, and a preponderance of point mutations. These data suggest that some of the components of the machinery are shared between ectotherms and mammals. However, unique characters in particular species may have occurred by independent recruitment of novel factors onto the mechanism. A spotty phylogenetic distribution of gene conversion has also been revealed and can be explained if the two mechanisms share some characteristics. Both mutation and conversion require transcription-related sequences and/or factors. We theorized that targeting to V genes can be attained by a paused replication fork that has collided with a transcription complex stalled by a defective Ig transcription activator; the paused replication fork results in recruitment of an error-prone translesion synthesis DNA polymerase (somatic hypermutation) or of DNA repair mechanisms with homologous recombination (gene conversion). In addition, the pathway recruited in different species may be directed by the degree of homology among V genes.
抗原受体基因的体细胞超突变实例可见于包括软骨鱼在内的大多数脊椎动物谱系中。对系统发育数据的分析表明，大多数被研究物种的该机制具有两个显著特征：突变热点序列AGY以及点突变占优势。这些数据表明，该机制的某些组成部分在外温动物和哺乳动物之间是共有的。然而，特定物种中的独特特征可能是通过将新因子独立招募到该机制上而出现的。基因转换的零散系统发育分布也已被揭示，如果这两种机制具有某些共同特征，那么这一点就可以得到解释。突变和转换都需要转录相关序列和/或因子。我们推测，靶向V基因可通过一个暂停的复制叉来实现，该复制叉与因有缺陷的Ig转录激活因子而停滞的转录复合体发生了碰撞；这个暂停的复制叉会导致招募易出错的跨损伤合成DNA聚合酶（体细胞超突变）或具有同源重组的DNA修复机制（基因转换）。此外，不同物种中所招募的途径可能由V基因之间的同源程度所引导。
