Exonic Transcription Factor Binding Directs Codon Choice and Affects Protein Evolution

Overview

Journal Science

Specialty Science

Date 2013 Dec 17

PMID 24337295

Citations 146

Authors

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

Affiliations

Soon will be listed here.

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.

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