Towards an evolutionary model of transcription networks.
Bottom Line: Evolutionary events on the DNA sequence that led to turnover of TF binding sites were identified, including a birth of an Oct4 binding site by a 2nt deletion.In contrast to recent reports of large interspecies differences of TF binding sites and gene expression patterns, the interspecies difference in TF-target relationship is much smaller.The data showed increasing conservation levels from genomic sequences to TF-DNA interaction, gene expression, TN, and finally to morphology, suggesting that evolutionary changes are larger at molecular levels and smaller at functional levels.
Affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.Show MeSH
Related in: MedlinePlus
Mentions: Some TFs are evolutionarily younger than others. We asked whether the divergence time of a TF from its ancestor is correlated with its re-wiring rate. The re-wiring rate of a TF is defined as the percentage of non-conserved TF-target links among all TF-target links of a TF. Since our model infers the target genes of a TF in every species fed to the model, re-wiring rate can be directly derived from the model output. An extensive survey of TFs that may regulate cell fate decisions in mouse PED reported 29 TFs , among which there were two sets of paralogous genes including Gata3/Gata4/Gata6 and cMyc/nMyc [Figure 5]. Using the HKY DNA substitution model  implemented in TreeFam , we inferred the divergence time of each TF to the closest common ancestor of the paralogous group [Figure 5B,C]. In all four comparisons (cMyc vs. nMyc, Gata4 vs. Gata3, Gata6 vs. Gata3, Gata6 vs. Gata4), the TF with a shorter divergence time always showed a smaller re-wiring rate (the largest pairwise comparison p-value<1E-10), suggesting in mammalian PED, evolutionary younger TFs are more likely to change their regulatory targets.
Affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.