Conditional mutations

Figure 49-13. Simplified scheme of the causation of familial hypertrophic cardiomyopathy (MIM 192600) due to mutations in the gene encoding fi-myosin heavy chain. Mutations in genes encoding other proteins, such as the troponins, tropomyosin, and cardiac myosin-binding protein C can also cause this condition. Mutations in genes encoding yet other proteins (eg, dystrophin) are involved in the causation of dilated cardiomyopathy.

Sierra, L.M., A.R. Barros, M. Garcia, J.A. Ferreiro, and M.A. Comendador. 1991. Acrolein genotoxicity in Drosophila melanogaster. I. Somatic and germinal mutagenesis under proficient repair conditions. Mutat. Res. 260 247-256. 

Trivedi. Cytogenetic surveillance of tobacco-arecanut (mava) chewers, including patients with oral cancers and premalignant conditions. Mutat Res 1991 261(1) 41-49. 

In order to compare mutation frequency induced by 220-MeV C ions with that by low-LET radiation (electrons), Arabidopsis visible phenotype loci were chosen as follows transparent testa tt) whose seed coat is transparent because of lack of pigment glaborous gl), which have no hair on their leaves and stems and long hypocotyl hy) whose hypocotyl is longer than that of the wild type in the light condition. Mutation frequencies of tt, gl, and hy induced by carbon ions were 8- to 34-fold higher than those by electrons (Table 2). In this study, irradiation doses for the induction of mutation were determined from the RBE of carbon ions compared with that of electrons on the survival of plants, which was approximately 5. Both doses are at three-quarters of the shoulder dose of each survival curve [104]. 

WY Chow, DE Berg. Tn5tacl, a derivative of transposon Tn5 that generates conditional mutations. Proc Natl Acad Sci (USA) 85 6468-6472, 1988. 

Conditional Mutation. Phenotype of the organism changes only under a specific condition called the restrictive condition, but remains normal under other conditions called the permissive condition. 

Temperature-Sensitive Mutation. It is a special case of conditional mutation in which the restrictive condition is elevated or lowered temperature. Temperature-sensitive mutants are commonly used to analyze the function of essential genes, because inactivating mutations such as deletion mutations are not possible for these genes. 

The mechanism by which sublethal or conditional mutations in so many genes result in inositol auxotrophy still remains to be explained. However, it is clear that INOl transcription is exquisitely sensitive to even minor perturbations of the global transcriptional apparatus (reviewed in Henry and Patton-Vogt, 1998). This fact no doubt provides at least a partial explanation for the... 

Scafe, C., Martin, C., Nonet, M., Podos, S., Okamura, S., and Young, R.A., 1990b, Conditional mutations occur predominantly in highly conserved residues of RNA polymerase II subunits. Mol. Cell. Biol. 10 1270-1275. 

Conditional Mutations Can Be Used to Study Essential Genes in Yeast... 

In haploid yeast cells, essential genes can be studied through the use of conditional mutations. Among the most common conditional mutations are temperature-sensitive mutations, which can be Isolated in bacteria and lower eukaryotes but not in warm-blooded eukaryotes. For Instance, a mutant protein may be fully functional at one temperature (e.g., 23 °C) but completely inactive at another temperature (e.g., 36 °C), whereas the normal protein would be fully functional at both temperatures. A temperature at which the... 

C. F. Arlett and S. A. Harcourt, The induction of 8 azaguanine-resistant mutants in cultured Chinese hamster cells by ultraviolet light. The effect of changes in post-irradiation conditions, Mutat. Res. 14, 431 (1972). 

Toxic agents, drugs, and other conditions Mutations due to ... 

Although the native protein can be used in the branched-photocycle architecture, it is ineffective and improvements are necessary. The quantum efficiency of the O —> P photoconversion ( 2 x 10" ) is low, and the O state has a low yield ( 1 to 3% under ambient conditions). Mutations directed at optimizing these two photophysical properties suggest that significant improvements can be made to enhance conversion into the branched photocycle intermediates. Site-directed mutants were created that enhance the yield of the O state and the quantum efficiency of the O —> P photoreaction. However, site-directed mutants are restricted to knowledge of the protein based on modeling information. Because there are many aspects of the photocycle yet to be discovered, more randomized mutagenesis methods are necessary to complete the optimization process. A summary of optimization methods is shown in Table 135.2. 

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