Frameshift mutations The genetic message, once initiated at a fixed point, is read in a definite frame in a series of three letter words. The framework would be disturbed as soon as there is a deletion or addition of one or more bases. There is evidence that mutations induced by acridine dye and related compounds depend on addition or deletion of single bases. When such frameshift mutations were intercrossed, in certain combinations they gave wild type. It was concluded that one of them was deletion and the other an addition, so that the disturbed order of the frame due to one mutation will be restored by the other (Fig. 30.6). In such a restoration, a few amino acids coded by mRNA segment lying between the sites of deletion and addition would differ from those in normal protein. These differences could be-explained on the basis of the Genetic Code and, therefore, are used as an evidence in favour of the properties described for Genetic Code.

Fig. 30.6. Frame-shift mutations due to deletion and addition.

Base substitutions or amino acid replacements
If in a mRNA at a particular point, one base pair is replaced by another without any deletion or addition, the meaning of one codon containing this altered base will change as discussed in Mutations: 3.  Molecular Level (Mechanism). Consequently, in place of a particular amino acid at a particular position in a polypeptide, another amino acid will be incorporated. Such mutations have been studied in detail in enzyme tryptophan synthetase. By working out the altered amino acid sequences in the polypeptides, some conclusions regarding the possible changes in the base-sequence in RNA can be easily made, if the dictionary of genetic code is available. This has been done inJryptophan synthetase and also in case of haemoglobin using sickle cell anemia. More details about these mutations are given in Mutations: 3.  Molecular Level (Mechanism) and also later in this section, while discussing suppressor mutations. All such mutations could be easily explained on the basis of the Genetic Code dictionary given-in Figure 30.4. The mutations thus provide an evidence to suggest that the Genetic Code deciphered in cell free system holds good in living cells also.

Fig. 30.4. Genetic code dictionary.