Dynamical consequences of context-dependent mutation: visualizing antibody sequence evolution during somatic hypermutation

Context-dependent, non-reversible somatic hypermutation in antibody antigen-binding regions yields long-term sequence dynamics that recover hot- and cold-spot patterns while revealing substantial heterogeneity in mutability.

• Why it matters: Local sequence-context biases are known to affect substitution rates, but their cumulative impact across many mutational steps on sequence evolution is difficult to visualize and quantify.
• What they did: The study develops a framework to analyze long-term dynamics from context-dependent mutation rates and applies it to inferred somatic hypermutation during affinity maturation across antibody-encoding gene families.
• The result: Mutational biases propagate from 5-nucleotide contexts to codon and amino acid levels, producing low stationary frequencies for stop codons and tyrosine and high stationary frequencies for proline, consistent with naive-to-memory B-cell amino-acid composition changes.