Question

Describe a tautomeric shift and how It may lead to a mutation.

Short answer

Answer: A tautomeric shift is a chemical reaction in which a molecule undergoes an isomerization that results in the transfer of a hydrogen atom between two sites within the molecule. In genetics, tautomeric shifts involve nitrogenous bases in nucleic acids, which can cause mispairing during replication or transcription, ultimately leading to mutations. These shifts can be classified into two types: keto-enol and amino-imino. Tautomeric shifts can lead to mutations by causing a change in the hydrogen-bonding properties of the affected nitrogenous base, resulting in non-standard base-pairing interactions and incorporation of incorrect nucleotides.

Step-by-step solution

Introduction to Tautomeric Shifts

A tautomeric shift is a chemical reaction in which a molecule undergoes an isomerization (rearrangement of atoms) that results in the transfer of a hydrogen atom between two sites within the molecule. In the context of genetics, tautomeric shifts involve nitrogenous bases in nucleic acids (DNA and RNA), which can cause mispairing during replication or transcription, ultimately leading to mutations.

Types of Tautomeric Shifts

Tautomeric shifts can be classified into two main types: keto-enol and amino-imino shifts. In a keto-enol shift, the hydrogen atom is transferred between a carbonyl group (keto form) and an adjacent hydroxyl group (enol form) within the molecule. This type of shift mainly affects the pyrimidine bases (Cytosine and Thymine) in DNA. In an amino-imino shift, the hydrogen atom is moved between a nitrogen atom in an amino group and an adjacent nitrogen atom, forming an imino group. This shift mainly affects purine bases (Adenine and Guanine) in DNA.

Tautomeric Shifts and Mutations

Tautomeric shifts can lead to mutations by causing a change in the hydrogen-bonding properties of the affected nitrogenous base. These changes can result in non-standard ("wobble") base-pairing interactions during the replication or transcription process, leading to the incorporation of incorrect nucleotides. For example, a tautomeric shift of cytosine from its keto to enol form leads to a change in its hydrogen-bonding properties, causing it to pair with adenine instead of guanine. This event can result in a base substitution (point mutation), specifically a transition mutation, where a pyrimidine base is replaced by another pyrimidine base (C to T) or a purine base by another purine base (A to G).

Example of a Tautomeric Shift Leading to Mutation

Consider the following DNA sequence: 5'-AATTCCGG-3'. During replication, a tautomeric shift occurs, causing cytosine (C) at position 5 to undergo a keto-enol shift, resulting in non-standard base-pairing with adenine (A) on the newly synthesized strand. This event will lead to the following mutated sequence: 5'-AATT A GGG-3'. In this case, the original cytosine has been replaced by thymine, resulting in a point mutation. This mutation could potentially alter the function or structure of the corresponding protein encoded by this DNA sequence, leading to various biological effects, including genetic disorders or disease.