The targeting of somatic hypermutation.
The targeting of somatic hypermutation.
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DOI：
10.1006/smim.1996.0020
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发表时间：
1996-06-01
影响因子：
7.8
通讯作者：
Neuberger, M S
中科院分区：
文献类型：
--
作者：
Jolly, C J;Wagner, S D;Neuberger, M S
体细胞超突变不会随机发生在免疫球蛋白V基因内，而是优先靶向某些核苷酸位置（热点）并远离其他位置（冷点）。冷点通常与V基因折叠所必需的残基一致。热点，似乎是战略性地定位以有利于亲和力成熟，最常见的是位于CDR（特别是CDR 1），尽管保守的热点也发现在FR 3的基础上。热点部分由局部DNA序列产生，并且V基因中密码子使用的强烈偏好表明基因已经进化，使得体细胞超突变针对V的那些可能被证明最有用的部分。突变热点和偏向密码子使用的这些特征在低等动物的V基因中也很明显，这表明通过非模板突变的战略靶向的多样化可能在抗原受体进化的早期就已经进化了。
Somatic hypermutation does not occur randomly within immunoglobulin V genes but, rather, is preferentially targeted to certain nucleotide positions (hot spots) and away from others (cold spots). Cold spots often coincide with residues essential for V gene folding. Hotspots, which appear to be strategically located to favour affinity maturation, are most frequently located in the CDRs (particularly CDR1) though conserved hotspots are also found at the base of FR3. Hotspots are in part created by local DNA sequence and the strong biases of codon usage in V genes indicate that the genes have evolved such that somatic hypermutation is targeted to those parts of the V where it is likely to prove most useful. These features of mutational hotspots and biased codon usage are also evident in V genes of lower animals suggesting that diversification by strategic targeting of non-templated mutation may have evolved early in antigen receptor evolution.