Seeing double: appreciating genetic redundancy.

Genetic and molecular analyses of developmental and physiological processes in numerous experimental systems have recently revealed unsuspected levels of complexity within genetic regulatory pathways. Perhaps most surprising is the result that loss-of-function mutations engineered within many regulatory genes have little or no effect on phenotype. Although the lack of phenotype suggests that these genes are not essentia1 to the processes under consideration, new evidence indicates that these mutations are partly or completely compensated for by the activity of other genes. Genes whose products are capable of compensating for the loss of other gene activities are said to display redundant (or partially redundant) genetic function. Recent evolutionary studies suggest that redundancy may be both an inevitable result of genome evolution and an aspect of the informationalcomplexity found within phylogenetic lineages in which ancient tetraploidization events occurred. The fact that genetic redundancy has been encountered in many different pathways suggests that the modification of experimental designs to account for redundancy should result in the more complete genetic characterization of cellular and developmental processes. Redundant gene activity appears to occupy a continuum from the complete redundancy seen between duplicated housekeeping genes to the partial overlap of function seen in a number of regulatory genes that influence developmental processes. This continuum could be extended to include initially redundant genes (arising by gene duplication, for instance) that have evolved completely independent functions through the acquisition of new functions. In some cases, two genes have a redundant function in a subset of developmental or cellular processes but have independent functions in other processes. This observation suggests a link between pleiotropy (a requirement for a gene’s activity at more than one developmental stage or in more than one cellular process) and redundancy. Recent experiments in plants and animals also indicate that many genes function in complex “information networks,” with cross-talk between regulators and/or feedback loops. Such interactions provide a sophisticated type of redundancy that is capable of maintaining pathway activity and