Somatic hypermutation patterns are shaped by both motif position and sequence grammar

ABSTRACT: Somatic hypermutation (SHM) in variable regions of immunoglobulin genes by activation-induced deaminase (AID) is essential for the maturation of protective antibodies against pathogen and vaccine antigens. AID preferentially mutates cytosines within WRCH motifs (wherein W = A/T, R = A/G, and H = A/C/T) in single-stranded DNA, yet these motifs show large but reproducible variation in mutation frequency, suggesting a crucial role for sequences flanking the WRCH motifs (i.e., a sequence grammar) in determining mutational outcomes. However, the nature of this sequence grammar is poorly understood. Here, we demonstrate that identical sequence contexts can exert significantly varying effects on the mutagenesis of different WRCH motifs. Molecular dynamics simulations reveal that both the sequence

SUBMITTER: Bianca Bartl 

PROVIDER: S-SCDT-10_1038-S44318-025-00640-9 | biostudies-other |

REPOSITORIES: biostudies-other