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What drives codon choices in human genes?

S Karlin¹, J Mrázek

¹Department of Mathematics Stanford University, CA 94305-2125, USA.

Journal of Molecular Biology

|October 4, 1996

Summary

Human codon usage is primarily driven by amino acid needs and DNA structural integrity, not just gene expression levels. This codon signature reflects genome-wide DNA processes, offering a new perspective on synonymous codon bias.

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Area of Science:

Genomics
Molecular Biology
Bioinformatics

Background:

Synonymous codon usage bias varies across organisms.
Factors influencing codon bias include gene expression, DNA composition, and protein-related constraints.

Purpose of the Study:

To propose a new perspective and methods for analyzing codon choices in the human genome.
To investigate the roles of amino acid constraints and DNA structural tendencies in human codon usage.

Main Methods:

Defining and analyzing codon signatures based on dinucleotide relative abundances.
Correlating codon signatures with genome-wide DNA modification, replication, and repair processes.
Evaluating codon usage estimates against actual usage in human and vertebrate genes.

Main Results:

Human codon choices are significantly influenced by amino acid constraints and DNA structural requirements.
Codon signatures, particularly at silent sites, reflect DNA symmetry and genome-wide dinucleotide underrepresentation (CG and TA).
Codon signature-based estimates align well with observed synonymous codon usage in humans and vertebrates, independent of G+C content or gene size.

Conclusions:

Human codon usage is shaped by a combination of protein-level residue preferences and DNA-level biases related to replication, repair, and structural needs.
The proposed codon signature offers a robust framework for understanding synonymous codon usage, accommodating both genomic and amino acid constraints.
This perspective moves beyond traditional explanations focusing solely on expression levels and transcription/translation efficiency.

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