Conditional Lethal Mutations as Experimental Tools


Conditional lethal mutations are changes in the sequence of genetic material, which kill the organism, but only when it faces certain environmental conditions; under other conditions, the organism can survive and grow. Such mutations are useful genetic markers for a variety of essential genes.

Keywords: mutation; gene–environment interaction

Figure 1.

Suppression of chain‐terminating mutations by secondary mutations in a transfer ribonucleic acid (tRNA) anticodon. (a) A tRNA molecule brings a lysine residue to the ribosome to add to the growing polypeptide chain. The tRNA molecules interpret the genetic code by specifically matching mRNA codons to corresponding amino acids. (b) A mutation that changes an amino acid‐encoding codon to a stop codon results in a truncated protein. This occurs because no tRNA in the cell can base pair with the mutant codon. Assuming this protein is essential, such a mutation would likely be lethal to the organism. (c) A matching mutation in a tRNA gene which mutates the anticodon to recognize the stop codon results in suppression of chain termination. If the lysine residue is not essential to the protein's function, the organism would be able to survive.

Figure 2.

Isopropyl‐β‐D‐thiogalactoside (IPTG), a genetic ‘switch’. (a) When IPTG is not present in the growth medium of the cell culture, the lac repressor protein is bound to the IPTG‐driven promoter. The repressor protein stops the RNA polymerase from binding and transcribing the transgene. (b) When IPTG is present in the growth medium, it binds the repressor protein, causing a conformational change. This change makes it impossible for the repressor to bind DNA. With the repressor released from the promoter, RNA polymerase can bind and transcription can occur.


Further Reading

Baker TA and Wickner SH (1992) Genetics and enzymology of DNA replication in E. coli. Annual Review of Genetics 26: 447–477.

Benzer S (1962) The fine structure of the gene. Scientific American (January).

Bergmann JE (1989) Using temperature‐sensitive mutants of VSV to study membrane protein biosynthesis. Methods in Cell Biology 32: 85–110.

Coombs KM (1998) Temperature‐sensitive mutants of reovirus. Current Topics in Microbiology and Immunology 233: 69–107.

Hayes W (1968) The Genetics of Bacteria and their Viruses, 2nd edn. New York: Wiley.

Lindsley DL and Grell EH (1972) Genetic variations of Drosophila melanogaster. Washington DC: Carnegie Institute of Washington.

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Black, A Kristine, and Singh, Shiva M(Apr 2001) Conditional Lethal Mutations as Experimental Tools. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000835]