Towards an evolutionary model of transcription networks.
Bottom Line: 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.The data also showed that evolutionarily older TFs are more likely to have conserved target genes, whereas younger TFs tend to have larger re-wiring rates.
Affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.Show MeSH
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.