Model Answer
0 min readIntroduction
Mutations are alterations in the nucleotide sequence of the genome of an organism. These changes can occur spontaneously or be induced by mutagens. Base substitutions, a common type of mutation, involve replacing one nucleotide with another. While substitutions within the same purine or pyrimidine family (transitions) are more frequent, transversion mutations – involving the replacement of a purine with a pyrimidine or vice versa – can also occur. These alterations can have significant consequences, ranging from no effect to complete loss of gene function. This answer will explain how the replacement of a purine by a pyrimidine can induce mutations, using sickle cell anemia as a demonstrative example.
Understanding Purines and Pyrimidines
DNA is composed of four nitrogenous bases: adenine (A) and guanine (G), which are purines, and cytosine (C) and thymine (T), which are pyrimidines. Purines have a double-ring structure, while pyrimidines have a single-ring structure. This structural difference is crucial for maintaining the double helix structure of DNA, where purines always pair with pyrimidines (A with T, and G with C) to ensure consistent width and stability.
Consequences of Purine-Pyrimidine Replacement
Replacing a purine with a pyrimidine disrupts this established pairing rule and alters the DNA’s geometry. This mismatch can lead to several consequences:
- Distortion of the DNA Helix: The altered base pairing causes a bulge or distortion in the DNA helix, affecting its stability and potentially interfering with replication and transcription.
- Mispairing during Replication: During DNA replication, the mismatched base pair can lead to further errors. The DNA polymerase may incorporate an incorrect base opposite the altered base, leading to a permanent mutation.
- Activation of DNA Repair Mechanisms: The mismatch is often recognized by DNA repair systems. However, if the repair mechanisms are faulty or overwhelmed, the mutation can become fixed.
- Frameshift Mutations (in coding regions): If the mutation occurs within a coding region, it can lead to a frameshift mutation if it doesn't result in a stop codon. This alters the reading frame of the genetic code, resulting in a completely different amino acid sequence downstream of the mutation.
Sickle Cell Anemia: A Classic Example
Sickle cell anemia provides a compelling example of how a single base substitution – specifically, a purine-pyrimidine replacement – can induce a significant mutation. The disease is caused by a point mutation in the β-globin gene, where adenine (A) is replaced by thymine (T) in the sixth codon. This changes the codon from GAG (glutamic acid) to GTG (valine).
The Molecular Mechanism: The substitution of adenine (purine) with thymine (pyrimidine) alters the codon, leading to the incorporation of valine instead of glutamic acid at the sixth position of the β-globin chain. This single amino acid change causes the hemoglobin molecules to polymerize under low oxygen conditions, forming long, rigid fibers that distort the red blood cells into a sickle shape.
Consequences of the Mutation: The sickled red blood cells are less flexible and can block small blood vessels, leading to pain, organ damage, and anemia. This demonstrates how a seemingly small change at the molecular level can have profound physiological consequences.
| Normal β-globin Gene | Mutated β-globin Gene |
|---|---|
| DNA Sequence: ...GAG... | DNA Sequence: ...GTG... |
| mRNA Sequence: ...GAG... | mRNA Sequence: ...GTG... |
| Amino Acid: Glutamic Acid | Amino Acid: Valine |
Other Mechanisms & Considerations
It's important to note that the consequences of a purine-pyrimidine replacement depend on several factors, including the location of the mutation (coding vs. non-coding region), the specific bases involved, and the efficiency of DNA repair mechanisms. Mutations in non-coding regions may affect gene regulation, while mutations in coding regions can alter protein structure and function. Furthermore, the cellular context and the presence of other mutations can also influence the phenotypic outcome.
Conclusion
In conclusion, the replacement of a purine by a pyrimidine represents a significant disruption to the normal structure and function of DNA. This mismatch can lead to distortions in the DNA helix, mispairing during replication, and ultimately, altered protein synthesis. Sickle cell anemia serves as a powerful illustration of how a single purine-pyrimidine substitution can have devastating consequences, highlighting the critical importance of maintaining the integrity of the genetic code. Understanding these molecular mechanisms is crucial for developing strategies to prevent and treat genetic diseases.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.