Chapter 19, Problem 1Q

Summary Introduction

To review:

The sequence of the following synthetic mRNA:

5’-AUG UCU CCU ACU GCU GAC GAG GGA AGG AGG UGG CUU AUC AUG UUU-3’

The type and effect of mutation in the following polypeptide products:

a. 5’-AUG UCU CCU ACU UGC UGA CGA GGG AAG GAG GUG GCU UAU CAU GUU U-3’

b. 5’-AUG UCU CCU ACU GCU GAC GAG GGA GGA GGU GGC UUA UCA UGU UU-3’

c. 5’-AUG UCU CCU ACU GCU GAC GAG GGA AGG AGG UGG CCC UUA UCA UGU UU-3’

d. 5’AUG UCU CCU ACU UGC UGA CGG AAG GAG GUG GCU UAU CAU GUU U-3’

Introduction:

Frameshift mutations result from the addition or deletion of one or a few base pairs within the reading frame. They alter the reading frame of all the base pair triplets present after the mutation site and hence are aptly named.

Explanation of Solution

Proteins are macromolecules, which are formed of one or more amino acid chains. Proteins are formed by the bond between two amino acids known as the amide bond or the peptide bond. The primary structure of a protein is an amino acid sequence. Three nucleotides in a reading frame are known as a codon. One codon codes for only one amino acid.

So, the sequence of a polypeptide coding

5’-AUG UCU CCU ACU GCU GAC GAG GGA AGG AGG UGG CUU AUC AUG UUU-3’

will be as follows:

5’-Met-Ser-Pro-Thr-Ala-Asp-Glu-Gly-Arg-Arg-Trp-Leu-Ile-Met-Phe-3’

a. Type of mutation in 5’-AUG UCU CCU ACU UGC UGA CGA GGG AAG GAG GUG GCU UAU CAU GUU U-3’: It is a type of deletion mutation, as the G nucleotide in the fifth codon in the original peptide is missing in this peptide. This leadsto an alteration in the amino acid sequence. The sixth codon in this peptide is UGA, which is a stop codon. This will lead to premature termination of translation. The sequence of this peptide will beasfollows:

5’-Met-Ser-Pro-Thr-Cys-3’

b. Type and effect of a mutation in 5’-AUG UCU CCU ACU GCU GAC GAG GGA GGA GGU GGC UUA UCA UGU UU-3’: This is a type of insertion mutation, as two G residues are introduced after GGA codons in the original peptide. The new amino acid sequence will be as follows:

5’-Met-Ser-Pro-Thr-Ala-Asp-Glu-Gly-Gly-Gly-Leu-Ser-Cys-Phe or Leu-3’

In place of Arg amino acid, glycine is present, which is a non-sense mutation. The rest of the polypeptide sequence is also changed.

c. Type and effect of a mutation in 5’-AUG UCU CCU ACU GCU GAC GAG GGA AGG AGG UGG CCC UUA UCA UGU UU-3’: In place of U in the 11^th codon, there is A, which is a transition mutation. The new amino acid sequence will be as follows:

5’-Met-Ser-Pro-Thr-Ala-Asp-Glu-Gly-Arg-Arg-Trp-Pro-Leu-Ser-Cys-Phe or Leu-3’

d. Type and effect of mutation in5’AUG UCU CCU ACU UGC UGA CGG AAG GAG GUG GCU UAU CAU GUU U-3’: In this peptide, U is inserted in 5 codons at first place, which leads to a change in the sequence of the polypeptide. In this polypeptide, the sixth codon is a stop codon. So, the peptide will be terminated pre-maturely. The sequence of this peptide will be as follows:

5’-Met-Ser-Pro-Thr-Cys-3’

Conclusion

Thus, it can be concluded that in the first peptide, there is a G nucleotide in the fifth codon, which leads to the introduction of the stop codon (UGA). In the second peptide, there is an insertion mutation. In the third peptide, there is a transition mutation. In the last peptide, there is an insertion of U in the 5^th codon. This forms a stop codon.