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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. 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?

  2. 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.

  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. Lysine is being produced in a lab-scale reactor by a threonine auxotroph. After 2 weeks of operation it was observed that the concentration of lysine in the reactor was gradually decreasing. Microbiological assays of reactor samples showed absence of contamination and recorded data showed no change in the operating conditions. The most probable reason for decrease in lysine concentration may be attributed to
  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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