Silent nucleotide substitutions and G + C content of some mitochondrial and bacterial genes

The G + C content of DNA varies widely in different organisms, especially microorganisms. This variation is accompanied by changes in the nucleotide composition of silent positions in codons. (Silent positions are defined and explained in the text). These changes are mostly neutral or near neutral, and appear to result from mutation pressure in the direction of increasing either A + T (AT pressure) or G + C (GC pressure) content. Variations in G + C content are also accompanied by substitutions at replacement positions in codons. These substitutions produce changes in the amino acid content of homologous proteins. The examples studied were genes for 13 mitochondrial proteins in five species, and A and B genes for bacterial tryptophan synthase in four species. In microorganisms, varying AT and GC mutational pressures, presumably resulting from shifts in the DNA polymerase system, exert strong effects on molecular evolution by changing the G + C content of DNA. These effects may be greater than those of random drift. The effects of GC pressure on silent substitutions in the systems examined are several times as great as the effects on replacement substitutions. GC pressure is exerted on noncoding as well as coding regions in mitochondrial DNA. This is shown by the close correlation (correlation coefficient, 0.99) of the G + C content of the noncoding D loop of mitochondria with the G + C content of silent positions in the corresponding mitochondrial genes.