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Three-dimensional eukaryotic genomic organization is strongly correlated with codon usage expression and function.

Alon Diament1, Ron Y Pinter2, Tamir Tuller3

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Functional similarity between genes, measured by codon usage frequency similarity (CUFS), strongly correlates with their 3D genomic distance in eukaryotes. This highlights the importance of three-dimensional genome architecture in gene organization.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Gene distribution in eukaryotic genomes is non-random, but links between gene function and genomic organization were previously weak.
  • Codon usage bias is known to influence gene expression and protein function across various stages.

Purpose of the Study:

  • To investigate the relationship between functional relatedness of genes and their three-dimensional (3D) genomic organization.
  • To introduce and apply a novel tool, codon usage frequency similarity (CUFS), for assessing functional relatedness.

Main Methods:

  • Utilized codon usage frequency similarity (CUFS) to quantify functional relatedness between genes based on codon and amino acid usage.
  • Analyzed chromosome conformation capture (3C) data to determine the 3D genomic distances between genes.
  • Applied the CUFS tool across multiple eukaryotic species: Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, mouse, and human.

Main Results:

  • A strong, direct correlation was observed between functional similarity (CUFS) and 3D genomic distance across all studied species.
  • This indicates that genes with similar codon usage patterns are located closer in the 3D genome structure.

Conclusions:

  • The 3D organization of eukaryotic genomes is crucial for gene function and organization.
  • Codon usage is tightly linked to genome architecture, suggesting a functional role for genomic spatial arrangement.