title: Exonic transcription factor binding directs codon choice and affects protein evolution.
abstract: Genomes contain both a genetic code specifying amino acids and a regulatory code specifying transcription factor (TF) recognition sequences. We used genomic deoxyribonuclease I footprinting to map nucleotide resolution TF occupancy across the human exome in 81 diverse cell types. We found that ~15% of human codons are dual-use codons ("duons") that simultaneously specify both amino acids and TF recognition sites. Duons are highly conserved and have shaped protein evolution, and TF-imposed constraint appears to be a major driver of codon usage bias. Conversely, the regulatory code has been selectively depleted of TFs that recognize stop codons. More than 17% of single-nucleotide variants within duons directly alter TF binding. Pervasive dual encoding of amino acid and regulatory information appears to be a fundamental feature of genome evolution.
authors: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors: Andrew B
authors: AB
authors: Stergachis
authors: Eric
authors: E
authors: Haugen
authors: Anthony
authors: A
authors: Shafer
authors: Wenqing
authors: W
authors: Fu
authors: Benjamin
authors: B
authors: Vernot
authors: Alex
authors: A
authors: Reynolds
authors: Anthony
authors: A
authors: Raubitschek
authors: Steven
authors: S
authors: Ziegler
authors: Emily M
authors: EM
authors: LeProust
authors: Joshua M
authors: JM
authors: Akey
authors: John A
authors: JA
authors: Stamatoyannopoulos
mesh_terms: D003062:Codon / Q000235:genetics*; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000737:chemistry; D019143:Evolution, Molecular; D059472:Exome; D005091:Exons; D015894:Genome, Human; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D003062:Codon; D014157:Transcription Factors; D003850:Deoxyribonuclease I