Change in CpG Context is a Leading Cause of Correlation between the Rates of Non-Synonymous and Synonymous Substitutions in Rodents

Abstract

Correlation between the rates of synonymous (silent) and non-synonymous (amino acid-changing) nucleotide substitutions in genes is a widespread and yet unexplained genome-level phenomenon, which is in disagreement with the neutral theory of molecular evolution (Kimura, 1983). Comparison of 7732 orthologous genes of mouse and rat confirms the previously observed correlation between the rates of substitutions in non-synonymous and synonymous nucleotide sites. In rodents, this correlation is primarily caused by tandem substitutions and, in particular, by CpG mutation bias leading to doublet nucleotide substitutions. The nature of correlation between the rates of synonymous and non-synonymous substitutions in seven pairs of prokaryotic genomes is unclear.