ArticleProceedings of the National Academy of Sciences of the United States of America2009
V-region mutation in vitro, in vivo, and in silico reveal the importance of the enzymatic properties of AID and the sequence environment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- A Viral Protein Antagonist for Both AID and APOBEC3.Viruses · 2026Review
- Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity.Frontiers in immunology · 2023Article
- Immunoglobulin somatic hypermutation in a defined biochemical system recapitulates affinity maturation and permits antibody optimization.Nucleic acids research · 2022Article
- Dynamic regulation of B cell complement signaling is integral to germinal center responses.Nature immunology · 2021Article
- Junctional and somatic hypermutation-induced CXCellular & molecular immunology · 2021Article
- Position-Dependent Differential Targeting of Somatic Hypermutation.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing data.PLoS computational biology · 2020Article
- AID-RNA polymerase II transcription-dependent deamination of IgV DNA.Nucleic acids research · 2019Article
- A Protein Antagonist of Activation-Induced Cytidine Deaminase Encoded by a Complex Mouse Retrovirus.mBio · 2019Article
- Random Walk Enzymes: Information Theory, Quantum Isomorphism, and Entropy Dispersion.The journal of physical chemistry. A · 2019Article
- Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation.Nature communications · 2018Article
- JMolecular immunology · 2018Article
- Mutations in human AID differentially affect its ability to deaminate cytidine and 5-methylcytidine in ssDNA substrates in vitro.Scientific reports · 2017Article
- Activation-induced deoxycytidine deaminase: Structural basis for favoring WRC hot motif specificities unique among APOBEC family members.DNA repair · 2017Article
- DNA polymerase ι functions in the generation of tandem mutations during somatic hypermutation of antibody genes.The Journal of experimental medicine · 2016Article
- Better living with hyper-mutation.Environmental and molecular mutagenesis · 2016Review
- Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification.DNA repair · 2016Article
- Activation-Induced Cytidine Deaminase Links Ovulation-Induced Inflammation and Serous Carcinogenesis.Neoplasia (New York, N.Y.) · 2016Article
- Practical guidelines for B-cell receptor repertoire sequencing analysis.Genome medicine · 2015Review
- The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Article
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7 authors.
Funding
Abstract
The somatic hypermutation of Ig variable regions requires the activity of activation-induced cytidine deaminase (AID) which has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) motif hot spots in in vivo and in vitro assays. We compared mutation profiles of in vitro assays for the 3' flanking intron of VhJ558-Jh4 region to previously reported in vivo profiles for the same region in the Msh2(-/-)Ung(-/-) mice that lack base excision and mismatch repair. We found that the in vitro and in vivo mutation profiles were highly correlated for the top (nontranscribed) strand, while for the bottom (transcribed) strand the correlation is far lower. We used an in silico model of AID activity to elucidate the relative importance of motif targeting in vivo. We found that the mutation process entails substantial complexity beyond motif targeting, a large part of which is captured in vitro. To elucidate the contribution of the sequence environment to the observed differences between the top and bottom strands, we analyzed intermutational distances. The bottom strand shows an approximately exponential distribution of distances in vivo and in vitro, as expected from a null model. However, the top strand deviates strongly from this distribution in that mutations approximately 50 nucleotides apart are greatly reduced, again both in vivo and in vitro, illustrating an important strand asymmetry. While we have confirmed that AID targeting of hot and cold spots is a key part of the mutation process, our results suggest that the sequence environment plays an equally important role.
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