Suppressor mutation
A suppressor mutation is a second mutation that alleviates or reverts the phenotypic effects of an already existing mutation in a process defined synthetic rescue. Genetic suppression therefore restores the phenotype seen prior to the original background mutation.[1] Suppressor mutations are useful for identifying new genetic sites which affect a biological process of interest. They also provide evidence between functionally interacting molecules and intersecting biological pathways.[2]
Intragenic vs. intergenic suppression
Intragenic suppression
Intragenic suppression results from suppressor mutations that occur in the same
Researchers showed that mutations caused by either a single base insertion (+) or a single base deletion (-) could be "suppressed" or restored by a second mutation of the opposite sign, as long as the two mutations occurred in the same vicinity of the gene. This led to the conclusion that genes needed to be read in a specific "reading frame" and a single base insertion or deletion would shift the reading frame (frameshift mutation) in such a way that the remaining DNA would code for a different polypeptide than the one intended. Therefore, researchers concluded that the second mutation of opposite sign suppresses the original mutation by restoring the reading frame, as long as the portion between the two mutations is not critical for protein function.[1]
In addition to the reading frame, Crick also used suppressor mutations to determine codon size. It was found that while one and two base insertions/deletions of the same sign resulted in a mutant phenotype, deleting or inserting three bases could give a wild type phenotype. From these results it was concluded that an inserted or deleted triplet does not disturb the reading frame and the genetic code is in fact a triplet.[1]
Intergenic suppression
Intergenic (also known as extragenic) suppression relieves the effects of a mutation in one gene by a mutation somewhere else within the
These Intergenic suppressions are also likely to persist in the population. When these compensatory mutations are established in organisms like E. coli making it resistant to the drug due to the presence of a drug, and the drug usage is halted, the resistant strains are not easily able to evolve back into strains that can then once again be sensitive to the drug they had incurred resistance to.[3] These strains are likely not subject to losing these compensatory mutations and which would greatly decrease the fitness in the strain resulting in the intermediate strains. These intermediate strains are subjected to bottlenecking and thus making it difficult for the alleles to be reverted prior to Intergenic suppressions. Consequently, when drugs are halted it can be seen that these mutations are likely to persist in the population.
Suppressor mutations also occur in genes that code for virus structural proteins. To create a viable
Revertant
In microbial genetics, a revertant is a mutant that has reverted to its former genotype or to the original phenotype by means of a suppressor mutation, or else by compensatory mutation somewhere in the gene (second site reversion).
See also
- Synthetic viability
References
- ^ a b c d e Hartwell, L. H., Hood, L., Goldberg, M. L., Reynolds, A. E., Silver, L. M., & Veres, R. C. (2008). Genetics: From Genes to Genomes. New York: McGraw-Hill.
- ^ a b Hodgkin J. Genetic suppression. 2005 Dec 27. In: WormBook: The Online Review of C. elegans Biology [Internet]. Pasadena (CA): WormBook; 2005-.
- ISBN 978-0-19-920746-6. Retrieved 27 April 2021.
- ^ PMID 4907266.