title: Codon equilibrium I: Testing for homogeneous equilibrium.
abstract: We present theoretical considerations that suggest that synonymous-codon usage might be expected to be close to an equilibrium distribution given a very homogeneous process of silent substitution. By homogeneous we mean that substitution depends only on the two bases involved, so that 12 base-substitution rates completely describe the silent substitution process. We have developed a method of statistically testing for such homogeneous equilibrium and applied it to reported data on the codon usages of different classes of organisms. Weakly expressed bacterial sequences and both mammalian and nonmammalian eukaryotic sequences deviate significantly from a random pattern of codon usage, in the direction of homogeneous equilibrium. On the other hand, highly expressed bacterial sequences do not exhibit homogeneous equilibrium, which may be correlated with recent experimental results showing that they are optimized to accept the most abundant tRNAs. To examine the effect of amino acid replacements on the homogeneous model of silent substitution, we divided the amino acids with degenerate codes into two classes, those with high mutabilities and those with low, and performed the same analysis on bacterial and eukaryotic data sets. The codon sets of the highly mutable class of amino acids are not further from homogeneous equilibrium than are the codon sets of the class with low mutabilities. We also found for the eukaryotic data that these independent classes of codon sets show very similar equilibrium patterns. The various results suggest a high level of uniformity in the process of silent fixation in the different synonymous-codon sets, especially in eukaryotes.
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D003062:Codon; D004247:DNA / Q000235:genetics; D005057:Eukaryotic Cells / Q000502:physiology; D005815:Genetic Code; D009154:Mutation; D011336:Probability; D011387:Prokaryotic Cells / Q000502:physiology; D012333:RNA, Messenger
chemical_list: D003062:Codon; D012333:RNA, Messenger; D004247:DNA