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Open Access Open Badges Research article

A codon substitution model that incorporates the effect of the GC contents, the gene density and the density of CpG islands of human chromosomes

Kazuharu Misawa

Author Affiliations

Research Program for Computational Science, Research and Development Group for Next-Generation Integrated Living Matter Simulation, Fusion of Data and Analysis Research and Development Team, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan

BMC Genomics 2011, 12:397  doi:10.1186/1471-2164-12-397

Published: 6 August 2011



Developing a model for codon substitutions is essential for the analyses of protein sequences. Recent studies on the mutation rates in the non-coding regions have shown that CpG mutation rates in the human genome are negatively correlated to the local GC content and to the densities of functional elements. This study aimed at understanding the effect of genomic features, namely, GC content, gene density, and frequency of CpG islands, on the rates of codon substitution in human chromosomes.


Codon substitution rates of CpG to TpG mutations, TpG to CpG mutations, and non-CpG transitions and transversions in humans were estimated by comparing the coding regions of thousands of human and chimpanzee genes and inferring their ancestral sequences by using macaque genes as the outgroup. Since the genomic features are depending on each other, partial regression coefficients of these features were obtained.


The substitution rates of codons depend on gene densities of the chromosomes. Transcription-associated mutation is one such pressure. On the basis of these results, a model of codon substitutions that incorporates the effect of genomic features on codon substitution in human chromosomes was developed.

Rate of molecular evolution; CpG hypermutability; codon substitution; gene density; chromosomal GC content