AID Hotspot Mutagenesis: Somatic Hypermutation

AID Activity

Scan speed 4 bp/s

Deamination rate (coldspot) 6%

Repair-pathway balance 40% error-prone

Mutation Spectrum

Mutations

At hotspot motifs

—

Transition : Transversion

0 : 0

Scan position

0 / 0

A T G C U (pending)

How it works

Activation-induced cytidine deaminase (AID) acts on single-stranded DNA exposed in the V-region during transcription in germinal-centre B cells. It converts cytosine to uracil by hydrolytic deamination:

C + H2O --AID--> U + NH3

AID does not hit every C equally — it strongly prefers the WRC motif (W = A/T, R = A/G, C = target), and the mirror-image GYW on the opposite strand. Per-base deamination probability used here:

P(mutate at i) = k_AID  if coldspot
P(mutate at i) = k_AID * 4  if WRC/GYW hotspot

Each U is a U:G mismatch. Two repair outcomes compete for it, set by the pathway-balance slider:

Replicate over U (faithful path) — DNA polymerase reads U as T during S-phase, fixing a C:G → T:A transition at that exact base.
Error-prone repair — UNG excises the uracil to an abasic site and MSH2/MSH6 mismatch-repair recruits translesion polymerases (Pol η, REV1). These insert a random base at the lesion (often a transversion, C:G → G:C or A:T) and frequently extend the error track onto a nearby A/T base, the hallmark of SHM's characteristic A:T mutation cluster.

Real affinity maturation repeats this cycle over many germinal-centre divisions, then Darwinian selection on the resulting antibody-affinity variants (not modeled here) keeps only the best binders — this simulation isolates the upstream mutagenesis step: where and how AID writes mutations into the V-region before selection ever acts on them.

Scanning V-region 5'→3'
AID pauses longest at WRC motifs

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