Based on its sequence similarity to Apobecl, which...

Based on its sequence similarity to Apobecl, which deaminates Cs to Us in RNA, activation-induced deaminase (AID) was originally proposed to work on RNA. But definitive experiments in $E$. coli demonstrated that AID deaminates Cs to Us in DNA. The authors of the paper expressed AID in bacteria and followed mutations in a selectable gene. They found that AID expression increased mutations about fivefold above the background level in the absence of AID expression. More importantly, they found that $80 \%$ of the induced mutations were $\mathrm{G} \rightarrow \mathrm{A}$ or $\mathrm{C} \rightarrow \mathrm{T}$. Does this fit with your expectation if AID-induced mutations arose by deamination of $\mathrm{C}$ to $\mathrm{U}$ in the DNA? [Hint: imagine what would happen if the G:U mismatch created by AID was replicated several times; how would the sequences of the final mutations relate to the original G-C base pair?

Based on its sequence similarity to Apobecl, which deaminates Cs to Us in RNA, activation-induced deaminase (AID) was originally proposed to work on RNA. But definitive experiments in $E$. coli demonstrated that AID deaminates Cs to Us in DNA. The authors of the paper expressed AID in bacteria and followed mutations in a selectable gene. They found that AID expression increased mutations about fivefold above the background level in the absence of AID expression. More importantly, they found that $80 \%$ of the induced mutations were $\mathrm{G} \rightarrow \mathrm{A}$ or $\mathrm{C} \rightarrow \mathrm{T}$. Does this fit with your expectation if AID-induced mutations arose by deamination of $\mathrm{C}$ to $\mathrm{U}$ in the DNA?
[Hint: imagine what would happen if the G:U mismatch created by AID was replicated several times; how would the sequences of the final mutations relate to the original G-C base pair?

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Key Concepts

DNA Replication and Mismatch Propagation

During DNA replication, if a uracil arising from deaminated cytosine is used as a template, it pairs with adenine. This mispairing results in a transition mutation; the original C:G pair is eventually replaced by a T:A pair upon subsequent rounds of replication. This process explains how an initial deamination event can propagate into a stable mutation in the genome.

Transition Mutations

Transition mutations refer to the substitution of a purine for a purine (or a pyrimidine for a pyrimidine), such as G to A or C to T. The pattern of mutations observed, where most were either G?A or C?T, aligns with the expected outcomes following the deamination of cytosine in DNA. The resulting mispairing during replication confirms that the deamination of C to U can lead predominantly to these specific transitions.

Cytosine Deamination

Cytosine deamination is a chemical reaction where a cytosine base loses an amine group to become uracil. In the context of DNA, this modification leads to a G:U mismatch because uracil pairs with adenine instead of guanine. This process is biologically significant because if the lesion is not repaired, it can result in fixation of mutations during DNA replication.

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