Exonic transcription factor binding directs codon choice and affects protein evolution

Andrew B. Stergachis, Eric Haugen, Anthony Shafer, Wenqing Fu, Benjamin Vernot, Alex Reynolds, Anthony Raubitschek, Steven Ziegler, Emily M. LeProust, Joshua M. Akey, John A. Stamatoyannopoulos

Research output: Contribution to journalArticle

157 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1367-1372
Number of pages6
JournalScience
Volume342
Issue number6164
DOIs
StatePublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

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    Stergachis, A. B., Haugen, E., Shafer, A., Fu, W., Vernot, B., Reynolds, A., Raubitschek, A., Ziegler, S., LeProust, E. M., Akey, J. M., & Stamatoyannopoulos, J. A. (2013). Exonic transcription factor binding directs codon choice and affects protein evolution. Science, 342(6164), 1367-1372. https://doi.org/10.1126/science.1243490