Exonic transcription factor binding directs codon choice and affects protein evolution

作者: A. B. Stergachis , E. Haugen , A. Shafer , W. Fu , B. Vernot

DOI: 10.1126/SCIENCE.1243490

关键词: Genetic codeTranscription factorCodon usage biasBiologyGeneticsDNA footprintingAmino acidGenome evolutionHuman genomeStop codon

摘要: Genomes contain both a genetic code specifying amino acids and regulatory 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. found that ~15% of codons are dual-use ("duons") simultaneously specify sites. Duons highly conserved have shaped protein evolution, TF-imposed constraint appears be major driver codon usage bias. Conversely, has been selectively depleted TFs recognize stop codons. More than 17% single-nucleotide variants within duons directly alter binding. Pervasive dual encoding acid information fundamental feature genome evolution.

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