Max-Planck-Institut für Biologische Kybernetik, Spemannstr. 38, D-72076 Tübingen,
The attitude of geneticists toward the genotype has oscillated throughout history. Pre-Mendelian animal and plant breeders considered the organism indivisible, even though they utilised the manifestations of genetic variability to their advantage for artificial selection. The rediscovery of Mendelian rules inspired a reductionist revolution in which genes were (more or less) considered independently, with evolution viewed as a change in gene frequencies. The genetic contribution to “phenotype” lies somewhere between these polar concepts1. As early as 1926, Chetverikov stressed the significance of gene interactions and the theory of an integrated genotype2. Most genes are tied together in balanced complexes which resist change in nature3. “Brute force” mutagenesis experiments designed to alter or remove single genetic elements often have drastic effects on this balance. Two important consequences (in addition to altering a “phenotype of interest”) are apparent to all who employ genetic dissection as a means of investigation: pleiotropy and genetic background effects. However, these are “bad words” for many and receive little attention in the neurogenetics literature. Pleiotropy results from gene action affecting more than one aspect of structure or function or both; and perhaps at more than one time during development4. Genetic background effects arise from polygenic variation and may indicate that a “gene of interest” contributes within a gene complex, typically giving rise to a “quantitative phenotype”. In this report, I describe changes in Drosophila brain gross anatomy observed in a collection of 29 central brain mutants following exchange of “original” genetic backgrounds with that derived from the “standard wild-type” Canton Special (CS) strain.
Placing mutations on a common genetic background is a procedure occasionally used in Drosophila to control for effects of polygenic variation5. Here, outcrossing was intended to permit comparisons of mutants with different “histories” in various behavioural paradigms. Interestingly, all outcrossed mutants showed changes in brain anatomy upon re-isolation. These included changes in specificity, expressivity, penetrance and various combinations thereof. Some mutants even appeared completely wild-type while others gradually shifted to new phenotypes.
These findings are important because they bear heavily on conclusions made about single genes “determining” aspects of nervous system development and behaviour - in Drosophila and in other species6. In neurogenetic and behavioural analyses, it is helpful to consider genetic background as part of the "heritable environment”7, controlling it as stringently as any parameter potentially influencing an experiment.