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Intragenic Suppression


Intragenic Suppression
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Suppression mutations are of two types, intragenic suppression and extragenic suppression. In intragenic suppression a mutation in a gene is suppressed by another mutation in the same gene.

The effects of a previous mutation in a cistron are removed or reduced by another mutation in the same cistron.

Intragenic suppression may be divided into several types.

(1) Intracodon suppression. A codon that has undergone a change as a result of mutation may undergo another mutation to a codon that is less harmful to enzyme function.

Thus mutation of GCU (alanine) to GAV (aspartate) may results in an inactive enzyme. A second mutation A-->U would give the codon GUU for valine and may restore enzyme activity partially or full.


Mutation GAU 2nd Mutation GUC

GCU ------> ------------------->

Alanine Active Enzyme Aspartate Inactive Enzyme Valine Active enzyme.

Since the deleterious effect of the first mutation is suppressed by another mutation within the codon, the suppression is called intracodon suppression


(2) Reading frame mutations. A second mutation at a different site in the gene may neutralize the effects of the first mutation. This results in an altered enzyme which differs from the wild type by only a few amino acids.

Thus the addition of a base a few steps away from an earlier deletion can suppress the effects of the deletion. This change is brought about by a shift in the reading frame opposite in direction to that caused by the first mutation.


The effects of a deletion and an addition are shown in the following hypothetical sequences:

mRNA GUU CUG UUU CCU CGA ACU GAC GCA AUC GGU A
Poly peptide --Val - Leu - Phe - Pro - Arg - Thr - Asp - Ala - Ile- Gly

Normal mRNA and polypeptide
-U
mRNA GUVCUG VUC CVC GAA CUG ACG CAA UGGGUA A
Poly peptide -   -Val - Leu - Phe - Pro - Arg - Thr - Asp - Ala - Ile- Gly

Deletion of U from the third codon causes a shift in reading frame (Phe is not affected because of degeneracy in the code). This results in changed amino acids (italics) and the protein becomes inactive

mRNA GUV CUG VUC CUC GAA CUG ACU GCA AUC GGU
Polypeptide - V al- Leu - Phe - Leu - Glu - Leu - Thr.. Ala - Ileu - Gly­


Addition of U restores the original reading frame beyond the point of addition. The amino acid sequence is normal, except for the few residues between the two mutations. The polypeptide may be partially or full active.

(3) Suppression can also take place by an amino acid substitution some distance away from the site of the primary mutation.

In the tryptophan synthetase A gene of E. coli a primary mutation (glycine àglu­tamic acid) resulted in a nonfunctional enzyme.

The effect of this mutation was corrected by a second mutation (tyrosine -->cysteine) taking place 36 amino acid residues away in the same gene.

This mutation restored the activity of the enzyme. Neither mutation by itself permits the synthesis of a functional enzyme.

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