A mutation in which there is deletion or insertion of one or a few nucleotides is called a frameshift mutation. The name is derived from the fact that there is a shift in the reading frame backward or forward by one or two nucleotides.
Addition or deletion of one or two bases results in a new sequence of codons which may code for entirely different amino acids. This results in a drastic change in the protein synthesized.
The protein is usually nonfunctional. It should be noted that if the reading frame shifts by three nucleotides, the resulting protein is normal, except that it may lack one amino acid or may contain an extra amino acid.
The site of the mutation has an important bearing on whether the protein formed will be slightly or drastically altered.
Since translation, takes place in the 5'-->3' direction, a frameshift mutation near the 3' end of the gene results in only the terminal part of-the polypeptide chain being altered. This may result in a functional protein.
The several variants of haemoglobin are believed to have arisen in this manner.
Deletion
Removal of one or a few bases from a nucleotide chain is called a deletion. It will be seen that the removal of even one base will throw the genetic message out of frame beyond the point of deletion.
A new sequence will be established. This will happen on deletion of any number of bases not divisible by three.
Original (wild type) message or reading frame
CAT GAT CAT GAT CAT GAT CAT
Deletion.
-c
CAT GAT ATG ATC ATG ATC AT
Message out of frame
Insertion.
The genetic message will be similarly disturbed if one or a few bases are added (insertion), provided that the number of such bases is not divisible by three.
+G
CAT GAT GCA TGA TCA TGA TCA T
Messageout of frame
If there is simultaneous deletion and addition of a base, then the message will be out of frame only in the triplets between the deletion and addition.
Deletion and insertion
-c +c
CAT GAT ATG ATC ATC GAT CAT
Message out of frame
Mutations can be explained by the following analogy. Suppose that the genetic message is contained in the sentence: THE MAN WHO HAS ONE EYE CAN SEE YOU. In this sentence each word consisting of three letters represents a codon.
If the letter W of WHO is removed (deletion) the sentence becomes
THE MAN HOH ASO NEE YEC ANS EEY OU-. The sentence is meaningless after the word MAN.
If the letter A is added after MAN (insertion), then also the sentence becomes meaningless after MAN. THE MAN A WH OHA SON EEY
ECA NSE EYO U-.
If the letter H of WHO is replaced by U (substitution) the sentence becomes: THE MAN WUO HAS ONE EYE CAN SEE YOU. In this case only one word, WUO, becomes meaningless.
If the letters of WHO are reversed (inversion) the sentence becomes: THE MAN OHW HAS ONE EYE CAN SFE YOU. In this case also only one word is meaningless (OHW).
If the letter W of WHO is removed and the letter Z is added after ONE (deletion and insertion) the sentence becomes: THE MAN HOB ASO NEZ EYE CAN SEE YOU. Only the words involving the deletion and the insertion are meaningless.