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Question

The RNA sequence below depicts the part of a 330 nucleotides long mRNA and it encodes the C-terminal portion of a protein. 

5'-... ... ... AAC ACC ACG ACC CAU GUG GCG AGA CGG UAG- 3' 

A mutation was identified in this RNA denoted as 322A$\to$U. This nucleotide change is represented by which of the following class(es) of mutation?

Mutation Identification: 322A→U

The question identifies a mutation at nucleotide position 322 in a 330-nucleotide mRNA sequence, changing Adenine (A) to Uracil (U). We need to determine the type(s) of mutation this represents.

Determining the Codon Change

  1. Identify Codon Location: The mRNA sequence provided is 5'-... AAC ACC ACG ACC CAU GUG GCG AGA CGG UAG -3'. The total length is 330 nucleotides. The sequence ends with the stop codon 'UAG' (nucleotides 328-330). Counting backwards, the codon 'AGA' occupies positions 322-324.
  2. Analyze the Mutation: The mutation is specified as $322A→U$. This means the first nucleotide of the 'AGA' codon (position 322) changes from 'A' to 'U'.
  3. Original and Mutated Codons:
    • Original Codon (positions 322-324): $AGA$
    • Mutated Codon (positions 322-324): $UGA$

Classifying the Mutation Type

  1. Classification based on Effect (Nonsense):
    • The original codon, $AGA$, codes for the amino acid Arginine (Arg).
    • The mutated codon, $UGA$, is a stop codon, signaling the termination of translation.
    • A mutation that changes an amino acid-coding codon into a stop codon is defined as a nonsense mutation.
  2. Classification based on Chemical Change (Transversion):
    • The specific nucleotide change is Adenine ($A$) to Uracil ($U$).
    • Adenine ($A$) is a purine base.
    • Uracil ($U$) is a pyrimidine base.
    • A mutation swapping a purine for a pyrimidine (or vice versa) is called a transversion mutation. (A purine-to-purine or pyrimidine-to-pyrimidine change is a transition).

Therefore, the mutation $322A→U$ is classified as both a nonsense mutation and a transversion mutation.

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Important Questions from Mutations and Mutagenesis

  1. Determine the correctness or otherwise of the following Assertion [a] and the Reason [r]. 
    Assertion [a]: Chromosome mutations can change the structure of chromosomes. 
    Reason [r]: All chromosome mutations arise due to nondisjunction of chromosomes during mitosis or meiosis.

  2. A DNA sequence, 5'-ATGGACGTGCTTCCCAAAGCATCGGGC-3', is mutated to obtain 

    P. 5'-ATGGACGTGCTTCaCAAAGCATCGGGC-3′ 

    Q. 5′-ATGGACGTGCTTCCCgAAAGCATCGGGC-3′ 

    R. 5'-ATGGACGTGCTTCC-AAAGCATCGGGC-3′ 

    S. 5'-ATGGACGTGCTTCCCAAtGCATCGGGC-3′ 

    T. 5'-ATGGACGaGCTTCCCAAAGCATCGGGC-3′ 

    [Point mutations are shown in the lower case or ‘–' within the sequences] 

    Which of the above mutant sequences DO NOT have frame-shift?

  3. A mutation in a gene that codes for a polypeptide results in a variant polypeptide that lacks the last three amino acids. What type of mutation is this?
  4. A truncated polypeptide is synthesized due to a nonsense mutation. Where would you introduce another mutation to obtain a full-length polypeptide?
  5. Determine the correctness or otherwise of the following Assertion (a) and the Reason (r). 

    Assertion : N-methyl-N'-nitro-N-nitrosoguanidine (NTG) is an effective chemical mutagen. 

    Reason: Mutations induced by NTG mainly are the GC $\rightarrow$ AT transitions.

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