title: A codon substitution model that incorporates the effect of the GC contents, the gene density and the density of CpG islands of human chromosomes.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. kazumisawa@riken.jp
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Misawa
mesh_terms: D001482:Base Composition; D002877:Chromosomes, Human / Q000235:genetics*; D003062:Codon / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D012044:Regression Analysis
chemical_list: D003062:Codon