Contextual genetics

Complex phenotypes result from multiple inputs from genetic and environmental sources, with intricate subsystems mediating the influence of both sources on the phenotype. Experiments that attempt to describe the influence of a particular gene involve partial isolation of the sub-system in which that gene is an element from other components of the total system influencing the phenotype. Any interactions that exist between the controlled variables and the processes downstream of the gene in the normally operating total system become undetectable; therefore, the results of the experiment can be restricted to the particular configuration of the controlled variables. The inescapable price of the precision of knowledge generated by experiment is a reduction in the generalizability of the results beyond the constrained circumstances of the particular experimental situation. Integrative research, permitting the influence of related subsystems, is required to provide a comprehensive assessment of the influence of a gene.     

Mitochondrial genetics

Summary Cytoplasmic petite mutants of Saccharomyces cerevisiae carrying the gene conferring the resistance to chloramphenicol on one hand and the gene conferring the resistance to erythromycin on the other, have been crossed with each other. The two types of petites differed in the buoyant densities of their mitochondrial DNA. A novel type of evidence has been adduced, that the two genes are indeed located on mitochondrial DNA. Diploid petite recombinants were found, carrying both genes and containing not a mixture of the two parental DNAs but a new species of mitochondrial DNA of intermediate buoyant density. Recombination of mitochondrial genes involves therefore breakage and reunion of DNA molecules. New suppressiveness, different from the two parental ones, can result from the recombination of mitochondrial DNA. Recombination between petite mutants implies that the mitochondrial recombination enzymes have to be synthesized on cytosol ribosomes.     

Hydrogenase genetics

The decreasing availability of energy resources has brought about a renewed interest in the enzyme hydrogenase. Hydrogen gas can be produced by organisms and represents a potential renewable energy source, or it can be utilized by certain organisms as a sole energy source during processes that result in the net fixation of carbon, a biosynthetic capability that might be exploited for the production of specific compounds. Both the production and utilization of hydrogen in biological systems are dependent on hydrogenase. The manipulation of the expression of hydrogenase in attempts to optimize hydrogen production or utilization will to a certain extent be dependent on existing knowledge concerning the regulation of hydrogenase and its interactions with other aspects of cellular metabolism. Information pertaining to the genetics of hydrogenases should play an important role in the construction of organisms affected in their hydrogen metabolism. The genetics of hydrogenase in enteric bacteria, in hydrogen bacteria, and in root nodule bacteria are reviewed, and the implications concerning the manipulation of hydrogenase genes are discussed.     

Chemical genetics: where genetics and pharmacology meet

Genetics and pharmacology can elicit surprisingly different phenotypes despite targeting the same protein. This Essay explores these unexpected differences and their implications for biology and medicine.