The transcriptomics of phenotypic nonspecificity in Drosophila melanogaster

Transcription factor (TF) function is redundant: TF phenotypes are frequently rescued by TFs not resident to the TF locus, a phenomenon termed phenotypic nonspecificity. Phenotypic nonspecificity in Drosophila melanogaster is not dependent on the DNA binding specificity of the TFs and generally due to genetic complementation. Two TF phenotypes (doublesex [dsx] and apterous [ap]) are rescued by multiple TFs. The rescue by resident TFs, and the rescue and non-rescue by non-resident TFs, of these two phenotypes were used to distinguish between three possible outcomes of the comparison of the TF-dependent mRNA accumulation in these two systems. First, the sets of TF-dependent mRNAs are independent and non-overlapping; second, the sets of TF-dependent mRNAs are independent and overlapping; and third, the sets of TF-dependent mRNAs are constrained and have extensive overlap. The transcriptomes associated with rescue by resident TFs, and rescue and non-rescue by non-resident TFs, of the two TF phenotypes (dsx and ap) provided many examples of extensive overlap indicating regulation of constrained sets of genes. However, the strength of correlation of transcript accumulation observed between the resident and non-resident TFs was not a strong predictor for rescue of the phenotype by the non-resident TFs. The regulation of a constrained set of genes supports the hypothetical assembly of TFs into wolfpacks, and not the hypothetical limited specificity of TF function, as a potential explanation of phenotypic nonspecificity. Article SummaryTranscription factors (TF) control the rate that the information stored in DNA is converted to RNA. Although often considered functionally very specific molecules, TF function is redundant, as frequently the process regulated by one TF is also be regulated by another unrelated TF; a genetic phenomenon termed phenotypic nonspecificity. This paper addresses what patterns of gene expression are brought about by TFs that can regulate, or not regulate, the processes of female abdomen pigmentation and initiation of wing formation. Surprisingly, the patterns of gene expression are very similar. Strangely though, the strength of similarity, or correlation, is not a strong predictor that the TF regulates the process.