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Tissue-specific codon usage and the expression of human genes.

Joshua B Plotkin1, Harlan Robins, Arnold J Levine

  • 1Harvard Society of Fellows and Bauer Center for Genomics Research, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA. jplotkin@fas.harvard.edu

Proceedings of the National Academy of Sciences of the United States of America
|August 18, 2004
PubMed
Summary

Synonymous codon usage differs between human tissues, suggesting translational control impacts gene regulation. Brain-specific gene codon usage was conserved in human and mouse evolution.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Tissue-specific protein levels are regulated by diverse mechanisms.
  • Research has primarily focused on transcriptional regulation.
  • The role of translational control in tissue-specific gene expression is less understood.

Purpose of the Study:

  • To investigate systematic differences in synonymous codon usage across six adult human tissues.
  • To examine the evolutionary conservation of codon usage in tissue-specific genes.
  • To explore the potential role of codon-mediated translational control in human tissue-specific gene regulation.

Main Methods:

  • Analysis of synonymous codon usage in genes selectively expressed in six adult human tissues.
  • Comparative genomic analysis of codon usage conservation between human and mouse brain-specific genes from their common ancestor.

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Main Results:

  • Identified systematic differences in synonymous codon usage between genes expressed in different human tissues.
  • Demonstrated selective preservation of codon usage in brain-specific genes throughout human and mouse evolution.

Conclusions:

  • Synonymous codon usage patterns vary significantly across human tissues.
  • Codon usage in brain-specific genes shows evolutionary conservation, suggesting functional importance.
  • Findings support the hypothesis that codon-mediated translational control plays a significant role in the differentiation and regulation of tissue-specific gene products in humans.