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The below mentioned article provide notes on reverse mutation.
When a mutation changes the wild type normal genotype to a mutant type, as is more often the case, the event is called a forward mutation. This is in contrast to reverse mutations in which the mutant genotype changes to the original wild type. In micro-organisms auxotrophs reverting to prototrophs are easily detected by plating cells of the originally auxotrophic strain on minimal medium.
In bacteriophage T4 the rll mutants (strains which cause rapid lysis of host cells) frequently revert to the wild type rll+ strain. In Drosophila a number of recessive mutant genes are known to revert to the wild type though with a lesser frequency than the forward mutations. The ability of mutant genes to revert suggests that mutation at least in some cases is not a permanent, irreversible process.
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Reverse mutations could occur in different ways. In a true reverse mutation, the original base pair sequence of the wild type may be restored. Thus if a GC pair of the wild type sequence is replaced by an AT pair to produce a forward mutation, a true reverse mutation could again substitute a GC pair in that position.
Sometimes a different base pair may be inserted at the site of the altered pair which had produced the forward mutation. Thus when GC is replaced by AT, the reversion may be due to substitution by CG instead of GC. This produces a reverse phenotype even though its sequence differs from the wild type in a single base pair.
Sometimes an apparently reverse mutation is due to a second suppressor mutation which suppresses the effect of the primary mutation so that the phenotype appears like the wild type. There may be intragenic suppression when the second mutation occurs within the gene carrying the first mutation but in a different site. Or suppression may be intergenic (extragenic) when the second mutation lies in a different gene.
In both types of suppression, the second suppressor mutation produces functional products of the gene which carries the first or primary mutation. For example suppose gene A is not able to produce A protein due to a mutation. A suppressor mutation in the same or in a different gene could result in the production of A protein, thereby reversing the mutation in gene A.
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In the case of intergenic suppression, the term suppressor gene denotes the gene which has the second mutation suppressing the primary mutation in another gene. The products of suppressor genes are usually components of the translation system; the suppressor molecules are frequently tRNA molecules.
In intragenic suppression, reversion to the normal phenotype might be caused by deletion and insertion of single nucleotides in the same gene. Thus if the reading frame of triplets is shifted due to a single deletion causing primary mutation, the frame would be restored if a single insertion occurs at the site of the second mutation.
Only the triplets between the deletion and insertion would add incorrect amino acids, the rest of the chain would be normal. If the site of the second mutation is close to the first, the number of wrong amino acids would be small, and a full length functional protein would be produced.
Intergenic suppression by suppressor genes is due to changes in the process of translation. Most of the suppressor genes result from mutations in the tRNA genes and their products are mutant tRNA molecules. There are suppressor genes for mutations in each of the three chain terminating codons namely amber (UAG), ochre (UAA) and opal (UGA).
Normally amber, ochre and opal are nonsense mutations located at sites within a message and result in fragments of polypeptide chains. The suppressor gene for each nonsense mutation allows insertion of an amino acid at the site of the nonsense codon and the chain is not terminated. The suppression of chain terminating mutants is brought about by reading of the nonsense codon as if it were a sense codon.
For example, one kind of amber suppressor inserts the amino acid tyrosine against the nonsense codon UAG. The suppressor gene produces a mutant tyrosine-specific tRNA. The normal tyrosine tRNA has the anticodon GUA and recognises the triplets UAC and UAU in mRNA. The anticodon in the mutant tRNA is changed to CUA which pairs with UAG and tyrosine is inserted instead of the chain terminating precociously.
Another example illustrates intergenic suppression in E. coli. A primary amber mutation in E. coli had changed a base triplet into a nonsense codon UAG. Some other cells of E. coli carrying the same mutation had an intergenic amber suppressor mutation in a gene coding for serine tRNA.
The suppressor gene produced mutant tRNA molecules with an altered anticodon that could recognise AUG. Thus the suppressor gene could insert serine at the site of the nonsense triplet AUG and full length polypeptide chains could be formed. Both UAG and UGA suppressors act by changing the anticodon in a specific tRNA and producing mutant suppressor tRNAs. The mechanism of UAA suppression is not fully known.
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The amber suppressor gene also explained the occurrence of conditional mutants in T4 bacteriophage. The amber mutants of T4 were found to grow on one strain of E. coli (called permissive host) but not in another strain (called restrictive host).
This was because the permissive strain of E. coli carried the amber suppressor gene which reversed the effect of the amber mutation. Cells of E. coli which do not have the amber suppressor gene also show the amber mutation.
