Chapter 15, Problem 1Q

Summary Introduction

To review:

The given deoxyribonucleic acid (DNA) sequences of two patients and to identify the kind of mutation and its effect in the protein formed after translation.

Given:

The coding sequences of beta-globin gene of two individuals suffering from mild anemia.

Person 1:

$\begin{array}{l}\text{Sequence 1: CCTTGGACCCAGAGGTTC}\hfill \\ \text{Sequence 2: CCTTGGACCTAGAGGTTC}\hfill \end{array}$

Person 2:

$\begin{array}{l}\text{Sequence 1: CCTTGGACCCAGAGGTTC}\hfill \\ \text{Sequence 2: CCTGGACCCAGAGGTTCT}\hfill \end{array}$

Introduction:

Mutation is essentially any persistent change in the nucleotide sequence of the genetic material of an organism. There are various types of mutations. Silent mutations alter the nucleotide sequence in a way that the final protein formed has its structure unchanged with respect to the normal protein sequence. A missense mutation refers to the point mutation, in which one nucleotide of the genetic sequence is altered resulting in a change in one amino acid of the protein sequence.

In case of a frame-shift mutation, a nucleotide is either added or deleted resulting in a complete change of the reading frame. Nonsense mutation refers to the kind, in which any codon, originally coding for a particular amino acid now codes for a stop codon due to a change in the nucleotide sequence.

Explanation of Solution

In the given coding sequences of person 1, the second sequence has a modified 10th nucleotide with respect to the first sequence. It has ‘T’ instead of ‘C.’ On converting this to ribonucleic acid (RNA) sequences, and then assigning amino acid to the codon in a reading frame, it was deduced that the 4th codon containing the transcribed 10th nucleotide was changed from GUC to AUC.

Thus, in the first sequence, the 4th codon coded for valine (amino acid) and the 4th codon of the second sequence coded for isoleucine (amino acid). Since a change in one nucleotide has resulted in a change in an amino acid of the protein chain it is missense mutation. The original amino acid chain is glycine-threonine-tryptophan-valine-serine-lysine and the changed amino acid sequence is glycine-threonine-tryptophan-isoleucine-serine-lysine.

Similarly, for the second person, the second sequence is modified by deletion of the 4th nucleotide. This has completely changed the reading frame. Now on translation, only the first codon is same in both the amino acid sequences. This is a type of frameshift mutation. The original amino acid chain is glycine-threonine-tryptophan-valine-serine-lysine and the changed amino acid sequence is glycine-threonine-tryptophan-isoleucine-serine-lysine.

Conclusion

Thus, it can be concluded that in the 2nd sequence of person 1, the nucleotide sequence has undergone a missense mutation resulting in different protein chain (glycine-threonine-tryptophan-isoleucine-serine-lysine). In the 2nd sequence of person 2, the nucleotide chain has been altered by a frameshift mutation resulting in glycine-threonine-tryptophan-isoleucine-serine-lysine amino acid sequence.