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

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Summary
This summary is machine-generated.

Approximately 15% of human codons are "duons," serving dual roles in specifying amino acids and regulating gene transcription. This dual coding profoundly impacts genome evolution and codon usage bias.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Genomes encode both amino acid sequences and regulatory elements like transcription factor (TF) binding sites.
  • Understanding the interplay between these two codes is crucial for deciphering genome function and evolution.

Purpose of the Study:

  • To investigate the prevalence and functional significance of dual-use codons (duons) that encode both amino acids and TF recognition sequences.
  • To determine the impact of duons on protein evolution, codon usage bias, and genetic variation.

Main Methods:

  • Genomic deoxyribonuclease I footprinting was employed to map TF occupancy at nucleotide resolution across the human exome.
  • Analysis was conducted in 81 diverse human cell types to capture a comprehensive view of TF binding.

Main Results:

  • Approximately 15% of human codons function as duons, specifying both amino acids and TF binding sites.
  • Duons are highly conserved, suggesting a significant role in shaping protein evolution and driving codon usage bias.
  • Over 17% of single-nucleotide variants within duons directly impact TF binding, highlighting their regulatory importance.
  • The regulatory code shows a depletion of TFs recognizing stop codons.

Conclusions:

  • Dual encoding of amino acid and regulatory information via duons is a fundamental characteristic of genome evolution.
  • TF-imposed constraints on duons are a major factor influencing codon usage bias.
  • Understanding duons provides new insights into gene regulation, protein evolution, and the impact of genetic variation.