A quantitative theory of directional mutation pressure proposed in 1962 explained the wide variation of DNA base composition observed among different bacteria and its small heterogeneity within individual bacterial species. The theory was based on the assumption that the effect of mutation on a genome is not random but has a directionality toward higher or lower guanine-plus-cytosine content of DNA, and this pressure generates directional changes more in neutral parts of the genome than in functionally significant parts. Now that DNA sequence data are available, the theory allows the estimation of the extent of neutrality of directional mutation pressure against selection. Newly defined parameters were used in the analysis, and two apparently universal constants were discovered. Analysis of DNA sequence has revealed that practically all organisms are subject to directional mutation pressure. The theory also offers plausible explanations for the large heterogeneity in guanine-plus-cytosine content among different parts of the vertebrate genome.

No abstract

A large amount of information has been collected on the base composition of deoxyribonucleic acid (DNA) and a compilation of the available data has been recently presented.' Several features may be briefly noted. Among the bacteria there exists a wide variation in the mean DNA base composition.2' I However, within each bacterial species the heterogeneity in the base composition is extremely small.4 In higher plants and animals the variation from species to species is considerably smaller than that found for the bacteria.' 6In the present paper, a unitary theory based on genetic and evolutionary considerations will be developed which attempts to account for the main characteristics of the distribution of DNA base composition in nature. A brief description of the theory has been presented in our previous paper.' The theory seems to be successful in the sense that it provides a consistent model which explains the stability of the mean base composition and the unimodal distribution of base composition among the DNA molecules from an organism.As a preliminary to the description of the theory, certain pertinent facts relevant to the variation and heterogeneity of DNA base composition will be recapitulated here:1. Among bacteria (possibly protozoa and algae also) the mean GC (guaninecytosine) content of DNA varies approximately from 25 to 75 per cent, and this range extends over the range of the mean GC content of DNA of higher organisms.2. Phylogenetic relations are reflected in the mean GC content. Thus, closely related organisms show similar base compositions. 6,7 3. Distribution of the GC content among the DNA molecules of an organism

When there are no biases in mutation and selection between the two strands of DNA, the 12 possible substitution rates of the four nucleotides reduces to six (type 1 parity rule or PR1), and the intrastrand average base composition is expected to be A = T and G = C at equilibrium without regard to the G + C content of DNA (type 2 parity rule or PR2). Significant deviations from the parity rules in the third codon letters of the four-codon amino acids result mostly from selective biases rather than mutational biases between the two strands of DNA during evolution. The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance. The present analysis shows that, although the PR2 violation is common in the third codon letters of four-codon amino acids, the contribution of PR2 violation to the DNA G + C content of the third codon position is small and, in majority of cases, mildly counteracts the effect of the directional mutation pressure on the G + C content.

No abstract