Silent genes

Many strains of Streptomyces peucetius produce daunomydn. These strains often cany a permanently repressed (silent) gene that codes for the enzyme duanomycin 14-hydroxylase. If this is reactivated by mutation, the daunomycin is further metabolised to produce a new antibiotics, 14-hydroxydaunomydn (adnamydn). 

A. Cornish Bowden and M. L. Cardenas, Silent genes given voice. Nature 409, 571 572... 

Another possibihty to gain the product encoded by a silent gene cluster can be achieved by a method called the in vitro reconstitution approach. A necessity is that the substrates of the pathway are predictable. The in vitro reconstitution of an entire biosynthetic pathway usually involves the separate overexpression of each gene, the purification of the resulting protein and the performance of enzymatic studies. Thus, the discovery of a fully elaborated metabolic product by this approach is likely to be very laborious. For example, after discovering a cryptic sesquiterpene synthase in the genome of S. coelicolor (64), the new epi-isozaene (8) could be produced successfully. This metabolite was shown to be an intermediate in the assembly line of the known Streptomyces sesquiterpene albaflavenone (9) (135). 

A further possibility in revealing products of silent gene clusters is the expression of putative pathway-specific activator genes upstream or within the putative cryptic biosynthetic gene clusters. This approach is based on the incorporation of an... 

Some of the small amounts of intracellular enzymes normally present in the plasma can be assumed to result from wear and tear of cells or overflow of enzyme from healthy cells. This contribution of enzymes to the circulating blood may decrease, either as the result of a genetic deficiency of enzyme production (e.g., as is the case for ALP in hypo-phosphatasia or in individuals homozygous for the silent gene for serum cholmesterase), or when enzyme production is depressed as a result of disease (e.g., the production of serum cholinesterase is often depressed in fiver disease). 

Columns 1 and 5 are based upon the nomenclature of Motulsky (M18) except where noted. In all cases where the EVE , EfE , and E iEl heterozygotes have been studied, the sub-type of the silent gene has not been determined. 

P Data for Americans of unspecified race (S32). The incidence figure is for all silent gene subtypes combined. 

Whittaker and Vickers (W23) reported a family in which the silent gene appeared to be segregating, but in which the amount of enzyme activity in some of the members was about half of that expected for the E E genotype. All members in two generations had DN and FN values which were characteristic of the usual phenotype. 

The discovery of an individual having no detectable serum cholinesterase activity was reported by Liddell et al. (L33) in 1962. Such individuals are said to possess a silent gene for cholinesterase, and to date, about 105 subjects have been reported to be homozygous for silent cholinesterase. Simpson and Kalow (S27) presented evidence that the silent cholinesterase gene is allelic to the usual cholinesterase gene. 

Most clear-cut and usually without ambiguity is the identification of subjects who have only the atypical, dibucaine-resistant variant in their plasma—that is, subjects who are either homozygous for at3q>ical esterase (EjEj) or heterozygous with one silent gene and one for at q>ical esterase (E-Et). 

A special problem is the certain identification of silent gene cases (EjE)). There are obviously several different point mutations that may render cholinesterase virtually inactive, but the distinction between these types at the present time would be entirely a matter of research. The immediate problem is always to establish whether a given person s lack of... 

Tlie analysis of the intracellular metabolites, the metabolome, by means of comparison of mutants metabolic profiles (comparative metabolomics) aids in understanding the networks of proteins and the presence of silent genes. 

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