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Science. 2013 Dec 13;342(6164):1367-72. doi: 10.1126/science.1243490.

Exonic transcription factor binding directs codon choice and affects protein evolution.

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  • 1Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.

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.

PMID:
24337295
[PubMed - indexed for MEDLINE]
PMCID:
PMC3967546
Free PMC Article
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