Computational Detection of Transcriptional Network Rewiring in Ascomycota Fungi

The upstream regulator of a group of functionally linked and co-regulated genes, a group known as a regulon, sometimes changes in related species. Nonetheless function and expression of the orthologous gene group across those Species is conserved. Specific cases of such transcriptional network rewiring have been characterized, but there are likely to be many more instances than have been reported so far. For example, it has been reported that Rap1 in Saccharomyces cerevisiae substituted Tbf1/Cbf1 in Candida albicans for ribosomal RP genes. A systematic computational approach to detect transcriptional network rewiring is needed to gain insight into evolutionary mechanisms as well as to interpret experimental results in related model organisms.  We develop a novel mathematical model and computational pipeline to detect rewiring of transcriptional networks where the Transcription Factor (TF) regulating a set of genes is replaced by another TF during evolution.  Our method is applied to evolutionarily conserved co-expressed gene groups across 23 yeast species for 126 TFs. Our dataset of Species includes Saccharomyces cerevisiae, Candida albicans and Ashbya gossypii.  The last one is economically important pathogen of cotton. Our method successfully detects TF substitution for the ribosomal RP regulon consisting of ribosomal RP genes. It is intriguing that sometimes a group of TFs appears to be switched with a second group of TFs for a group of genes.  For a group of 30 RP genes, we find six TFs that collectively switch with six other TFs for 10 most recently evolutionary diverged Species after the Whole Genome Duplication.