Codon usage affects the structure and function of the Drosophila circadian clock protein PERIOD

Jingjing Fu, Katherine A. Murphy, Mian Zhou, Ying H. Li, Vu H. Lam, Christine A. Tabuloc, Joanna C. Chiu, Yi Liu

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage “code” within genetic codons to regulate cotranslational protein folding.

Original languageEnglish (US)
Pages (from-to)1761-1775
Number of pages15
JournalGenes and Development
Issue number15
StatePublished - Aug 1 2016


  • Circadian clock
  • Codon usage
  • Drosophila
  • Period
  • Protein structure

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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