Suppressor mutation

A suppressor mutation is a second mutation that alleviates or reverts the phenotypic effects of an already existing mutation. 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 gene as the original mutation. In a classic study, Francis Crick (et al.) used intragenic suppression to study the fundamental nature of the genetic code. From this study it was shown that genes are expressed as non-overlapping triplets (codons).[1]

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 genome. The second mutation is not on the same gene as the original mutation.[2] Intergenic suppression is useful for identifying and studying interactions between molecules, such as proteins. For example, a mutation which disrupts the complementary interaction between protein molecules may be compensated for by a second mutation elsewhere in the genome that restores or provides a suitable alternative interaction between those molecules. Several proteins of biochemical, signal transduction, and gene expression pathways have been identified using this approach. Examples of such pathways include receptor-ligand interactions as well as the interaction of components involved in DNA replication, transcription, and translation.[1]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 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.
  2. ↑ 2.0 2.1 Hodgkin J. Genetic suppression. 2005 Dec 27. In: WormBook: The Online Review of C. elegans Biology [Internet]. Pasadena (CA): WormBook; 2005-.

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