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Open Access Highly Accessed Research article

Codon usage is associated with the evolutionary age of genes in metazoan genomes

Yosef Prat1, Menachem Fromer1, Nathan Linial12 and Michal Linial23*

Author Affiliations

1 School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel

2 Sudarsky Center for Computational Biology, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel

3 Deptartment of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel

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BMC Evolutionary Biology 2009, 9:285  doi:10.1186/1471-2148-9-285

Published: 8 December 2009



Codon usage may vary significantly between different organisms and between genes within the same organism. Several evolutionary processes have been postulated to be the predominant determinants of codon usage: selection, mutation, and genetic drift. However, the relative contribution of each of these factors in different species remains debatable. The availability of complete genomes for tens of multicellular organisms provides an opportunity to inspect the relationship between codon usage and the evolutionary age of genes.


We assign an evolutionary age to a gene based on the relative positions of its identified homologues in a standard phylogenetic tree. This yields a classification of all genes in a genome to several evolutionary age classes. The present study starts from the observation that each age class of genes has a unique codon usage and proceeds to provide a quantitative analysis of the codon usage in these classes. This observation is made for the genomes of Homo sapiens, Mus musculus, and Drosophila melanogaster. It is even more remarkable that the differences between codon usages in different age groups exhibit similar and consistent behavior in various organisms. While we find that GC content and gene length are also associated with the evolutionary age of genes, they can provide only a partial explanation for the observed codon usage.


While factors such as GC content, mutational bias, and selection shape the codon usage in a genome, the evolutionary history of an organism over hundreds of millions of years is an overlooked property that is strongly linked to GC content, protein length, and, even more significantly, to the codon usage of metazoan genomes.