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Codon usage between genomes is constrained by genome-wide mutational processes.

Swaine L Chen¹, William Lee, Alison K Hottes

¹Department of Developmental Biology, Stanford University School of Medicine, Beckman Center, B300, Stanford, CA 94304, USA. slchen@stanford.edu

Proceedings of the National Academy of Sciences of the United States of America

|March 3, 2004

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Genome-wide codon bias in bacteria, archaea, and eukaryotes can be predicted using two parameters derived from non-translated intergenic sequences. These parameters reflect mutational processes, not just selection on genes.

Area of Science:

Genomics
Molecular Biology
Evolutionary Biology

Background:

Codon bias, the non-uniform usage of synonymous codons, is a fundamental characteristic of genome sequences.
Understanding the drivers of codon bias is crucial for deciphering genome evolution and gene expression regulation.

Purpose of the Study:

To identify key parameters that determine genome-wide codon bias across diverse life forms.
To investigate whether codon bias can be predicted from non-translated genomic regions.

Main Methods:

Analysis of genome-wide codon bias in 100 eubacterial and archaeal organisms.
Calculation of two primary parameters: genome GC content and context-dependent nucleotide bias.
Assessment of parameter predictability using intergenic sequences in eubacteria, archaea, and eukaryotes (including mammals).

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Main Results:

Two parameters effectively differentiate codon bias in eubacteria and archaea, calculable from intergenic sequences.
Codon bias in nonmammalian eukaryotes is also predictable from intergenic sequences.
Mammalian codon bias is primarily influenced by the second parameter due to variable GC content across isochores.

Conclusions:

Genome-wide codon bias is predominantly shaped by genome-wide mutational processes.
Selective forces acting on translated sequences play a secondary role in determining overall codon bias.
Intergenic sequences provide valuable insights into the mutational underpinnings of codon bias across domains of life.