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Stergachis, Andrew B.; Haugen, Eric; Shafer, Anthony; Fu, Wenqing; LeProust, M.; Akey, Joshua M.; Stamatoyannopoulos, John A.
Science (American Association for the Advancement of Science), 12/2013, Letnik: 342, Številka: 6164Journal Article
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 exorne 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.
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