体细胞突变
胞苷脱氨酶
生物
基因
亲和力成熟
遗传学
DNA
外显子
活化诱导(胞苷)脱氨酶
抗体
突变
计算生物学
B细胞
作者
Yanyan Wang,Fei‐Long Meng,Leng-Siew Yeap
标识
DOI:10.1016/j.it.2024.01.005
摘要
Antibody-coding genes accumulate somatic mutations to achieve antibody affinity maturation. Genetic dissection using various mouse models has shown that intrinsic hypermutations occur preferentially and are predisposed in the DNA region encoding antigen-contacting residues. The molecular basis of nonrandom/preferential mutations is a long-sought question in the field. Here, we summarize recent findings on how single-strand (ss)DNA flexibility facilitates activation-induced cytidine deaminase (AID) activity and fine-tunes the mutation rates at a mesoscale within the antibody variable domain exon. We propose that antibody coding sequences are selected based on mutability during the evolution of adaptive immunity and that DNA mechanics play a noncoding role in the genome. The mechanics code may also determine other cellular DNA metabolism processes, which awaits future investigation.
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