regulatory network structure as a dominant determinant of transcription factor evolutionary rate监管网络结构作为转录因子进化速率的主要因素.pdfVIP

Regulatory Network Structure as a Dominant Determinant of Transcription Factor Evolutionary Rate 1 1,2,3 Jasmin Coulombe-Huntington *, Yu Xia * 1 Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America, 2 Department of Chemistry, Boston University, Boston, Massachusetts, United States of America, 3 Department of Biomedical Engineering, Boston University, Boston, Massachusetts, United States of America Abstract The evolution of transcriptional regulatory networks has thus far mostly been studied at the level of cis-regulatory elements. To gain a complete understanding of regulatory network evolution we must also study the evolutionary role of trans- factors, such as transcription factors (TFs). Here, we systematically assess genomic and network-level determinants of TF evolutionary rate in yeast, and how they compare to those of generic proteins, while carefully controlling for differences of the TF protein set, such as expression level. We found significantly distinct trends relating TF evolutionary rate to mRNA expression level, codon adaptation index, the evolutionary rate of physical interaction partners, and, confirming previous reports, to protein-protein interaction degree and regulatory in-degree. We discovered that for TFs, the dominant determinants of evolutionary rate lie in the structure of the regulatory network, such as the median evolutionary rate of target genes and the fraction of species-specific target genes. Decomposing the regulatory network by edge sign, we found that this modular evolution of TFs and their targets is limited to activating regulatory relationships. We show that fast evolving TFs tend to regulate other TFs and niche-specific proces