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

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Stergachis, Andrew B; Haugen, Eric; Shafer, Anthony; Fu, Wenqing; Vernot, Benjamin; Reynolds, Alex; Raubitschek, Anthony; Ziegler, Steven; LeProust, Emily M; Akey, Joshua M; Stamatoyannopoulos, John A
Year of Publication: 2013
Journal: Science
Volume: 342
Issue: 6164
Pagination: 1367-72
Date Published: 2013 Dec 13
Publication Language: eng
ISSN: 1095-9203
Keywords: Codon, Deoxyribonuclease I, DNA Footprinting, Evolution, Molecular, Exome, Exons, Genome, Human, Humans, Polymorphism, Single Nucleotide, Transcription Factors

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.

DOI: 10.1126/science.1243490
Alternate Journal: Science