Question

The Genetic Code and Mutation A mutation occasionally arises that converts a codon specifying an amino acid to a stop or nonsense codon. When this occurs in the middle of a gene, the resulting protein is truncated and often inactive. If the protein is essential, cell death can result. Which of these secondary mutations might restore some or all of the protein function so that the cell can survive (there may be more than one correct answer)? a. A mutation restoring the codon to one encoding the original amino acid b. A mutation changing the nonsense codon to one encoding a different but similar amino acid c. A mutation in the anticodon of a tRNA such that the tRNA now recognizes the nonsense codon d. A mutation in which an additional nucleotide inserts just upstream of the nonsense codon, changing the reading frame so the nonsense codon is no longer read as "stop"

Short answer

Options a, b, and c could restore protein function; option d is less likely.

Step-by-step solution

Identifying the Problem

The problem at hand involves identifying mutations that can remedy the effects of a nonsense mutation in the middle of a gene, leading to premature termination of protein synthesis. This results in a truncated and often inactive protein.

Understanding Mutation Types

There are several types of secondary mutations that can potentially restore functionality: reverting the mutation, allowing translation despite the stop codon, or altering the reading frame. Each of these is a potential solution based on the context provided.

Evaluating Option a

Option a describes a mutation that restores the original amino acid by correcting the codon. This would directly remedy the nonsense mutation by restoring the gene's original sequence, thus enabling normal protein synthesis.

Evaluating Option b

Option b suggests changing the stop codon to one that still encodes an amino acid, although it is different. This method won't produce the original protein, but if the similar amino acid does not drastically affect protein function, it might restore some function.

Evaluating Option c

Option c involves a mutation in the anticodon of the tRNA, allowing it to recognize and bind the premature stop codon, effectively enabling translation to continue. This bypasses the stop signal but requires the cell's translation machinery to recognize the altered tRNA.

Evaluating Option d

This option suggests introducing an additional nucleotide upstream of the nonsense codon, thereby altering the reading frame. This approach, however, could disrupt the sequence of amino acids downstream, resulting in a potentially non-functional protein even if it avoids the premature stop.

Conclusion of Solution Finding

The secondary mutations described in options a, b, and c could potentially restore some or all of the protein's function by either correcting or bypassing the nonsense mutation. Option d is less likely to succeed because frame shift changes could introduce significant errors in the protein's amino acid sequence.

Key concepts

Mutation

Mutations are changes that occur in the DNA sequence. They can happen due to errors during DNA replication or be induced by environmental factors. Mutations can vary in their effects on an organism depending on where they occur and what changes they lead to.

"Nonsense mutations" specifically disrupt protein synthesis by converting a normal codon that encodes an amino acid into a premature stop codon, also known as a nonsense codon. This truncates the protein, often rendering it inactive.

The impact of a mutation can range from benign to harmful. In some cases, like with nonsense mutations, it can be life-threatening if the protein affected is essential for survival. Understanding and identifying mutations that can nullify such negative effects is crucial for maintaining cellular function.

Nonsense Codon

A codon is a sequence of three nucleotides in mRNA that corresponds to a specific amino acid or stop signal during protein synthesis. Nonsense codons are special sequences that signal for the termination of protein synthesis.

• UAA
• UAG
• UGA

These codons do not code for any amino acids and hence, terminate translation prematurely. Their accidental introduction in the middle of a gene due to a mutation is the reason behind truncated proteins.

Truncated proteins are often dysfunctional, leading to potential loss of essential cellular activities. Understanding how nonsense codons work and how to manage their unexpected occurrence is essential in genetics and biotechnology.

Protein Synthesis

Protein synthesis is a fundamental process where cells build proteins. It occurs through two main stages: transcription and translation.

During transcription, a segment of DNA is copied into mRNA, which serves as a template for protein synthesis. Translation then interprets this mRNA sequence to align amino acids in the correct order, producing a polypeptide chain. This chain later folds into an active protein.

• Starts with the ribosome binding to mRNA.
• tRNA molecules bring corresponding amino acids based on codon specificity.
• Nonsense codons in mRNA lead to translation termination.

When nonsense mutations occur in mRNA, they prematurely halt this process, often resulting in inactive proteins. Understanding this helps in identifying genetic treatments and solutions.

tRNA

Transfer RNA (tRNA) is a key molecule involved in translation, the second stage of protein synthesis. It acts as an adaptor.

Each tRNA molecule has an anticodon region that pairs with a corresponding mRNA codon.

• tRNA molecules bring specific amino acids to the growing polypeptide chain.
• They ensure that the amino acids are added in the correct sequence.

In some cases, mutations in the tRNA anticodon can enable it to recognize a nonsense codon. This allows translation to "read through" the stop signal, potentially continuing protein synthesis beyond this point. However, this adaptation must be precise to avoid unintended effects.

Reading Frame

The reading frame refers to how nucleotides in mRNA are divided into codons, and it determines how the sequence is read during protein translation. Each codon consists of three nucleotides.

Altering the reading frame can dramatically change the interpretation of the genetic code. This usually happens through "frameshift mutations," which involve the insertion or deletion of nucleotides that are not a multiple of three.

• This shifts the entire sequence downstream.
• Different amino acids are coded, leading to abnormal proteins.

Sometimes a deliberate frameshift can negate a nonsense codon. However, this often leads to further complications, as it alters every codon beyond the mutation site. Correcting reading frames is a potential but risky approach in genetic engineering.