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Updated: Aug 14, 2026

An Integrated Approach for Microprotein Identification and Sequence Analysis
Published on: July 12, 2022
No evidence for tissue-specific adaptation of synonymous codon usage in humans
Marie Sémon1, Jean R Lobry, Laurent Duret
1Laboratoire de Biométrie et Biologie Evolutive (UMR 5558), Centre National de la Recherche Scientifique, Université Claude Bernard Lyon 1, Villeurbanne, France.
Abstract:
It has been proposed that the synonymous codon usage of human tissue-specific genes was under selective pressure to modulate the expression of proteins by codon-mediated translational control (Plotkin, J. B., H. Robins, and A. J. Levine. 2004. Tissue-specific codon usage and the expression of human genes. Proc. Natl. Acad. Sci. USA 101:12588-12591.) To test this model, we analyzed by internal correspondence analysis the codon usage of 2,126 human tissue-specific genes expressed in 18 different tissues. We confirm that synonymous codon usage differs significantly between the tissues. However, the effect is very weak: the variability of synonymous codon usage between tissues represents only 2.3% of the total codon usage variability. Moreover, this variability is directly linked to isochore-scale (>100 kb) variability of GC-content that affect both coding and introns or intergenic regions. This demonstrates that variations of synonymous codon usage between tissue-specific genes expressed in different tissues are due to regional variations of substitution patterns and not to translational selection.
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