Asymmetric evolution of human transcription factor regulatory networks

Changes in cis or trans regulatory regions are the major driving forces that underlie the evolution of gene expression. Transcription factors (TFs) are the main trans factors involved in transcriptional regulation. Here, we studied the divergence of upstream and downstream regulatory networks between duplicate TFs in light of the Encyclopedia of DNA Elements project. We found that the divergence of upstream regulatory networks was generally smaller than the divergence of downstream regulatory networks. Further analysis showed that the downstream regulatory circuits of duplicate TFs evolve faster in the early stage than the late stage after gene duplication. Upstream regulatory circuits are generally more conserved than downstream regulatory circuits in the early stage and in small TF families. Our results indicate the asymmetric evolution of upstream and downstream regulatory circuits between duplicate TFs, which suggest that after gene duplication, human TF families tend to evolve asymmetrically between coding regions and promoter regions.