Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution

Transcription Factor Binding Sites Transcription factors (TFs) are proteins that bind to DNA to control gene transcription. Stergachis et al. (p. 1367 ; see the Perspective by Weatheritt and Babu ) examined TF binding within the human genome in more than 80 cell types. Nearly 15% of coding regions simultaneously specify both amino acid sequence and TF recognition sites. The distribution of the TF binding sites evolutionarily constrains how codons within these regions can change, independent of encoded protein function. Thus, TF binding may represent a widespread and strong evolutionary force in coding regions.