Phenotypic Nonspecificity as the Result of Limited Specificity of Transcription Factor Function

Drosophila transcription factor (TF) function is phenotypically nonspecifc. Phenotypic nonspecifcity is defned as one phenotype being induced or rescued by multiple TFs. To explain this unexpected result, a hypothetical world of limited specifcity is explored where all TFs have unique random distributions along the genome due to low information content of DNA sequence recognition and somewhat promiscuous cooperative interactions with other TFs. Transcription is an emergent property of these two conditions. From this model, explicit predictions are made. First, many more cases of TF nonspecifcity are expected when examined. Second, the genetic analysis of regulatory sequences should uncover cis-element bypass and, third, genetic analysis of TF function should generally uncover diferential pleiotropy. In addition, limited specifcity provides evolutionary opportunity and explains the inefciency of expression analysis in identifying genes required for biological processes.