Silent substitutions in mammalian genomes and their evolutionary implications.

An analysis of silent substitutions in pairwise comparisons of homologous genes from different mammals has shown that, in spite of individual fluctuations, their frequencies (which are very strongly correlated with the frequency of substitutions per synonymous site calculated according to Li et al. 1985) do not vary, on the average, with the GC levels of silent positions. This holds in the general case, in which silent positions of pairs of homologous genes share the same composition, namely in the human/other primates, human/artiodactyls, and in the mouse/rat pairs, as well as in the special cases in which the composition of silent positions are different, namely in the human/rabbit and the human/rat (or human/mouse) pairs. A slightly lower frequency found for low GC values in the human/bovine and human/pig pairs seems to be due to the specific gene samples used. These results contradict the previously claimed existence of differences in mutation rates and of mutational biases in third codon positions of coding sequences located in different isochores of mammalian genomes. They also imply that the variations in nucleotide precursor pools through the cell cycle and the differences in replication timing, or in repair efficiency, which were reported for different isochores, do not lead, as claimed, to differences in mutation rates, not in mutational biases in mammals. The differences claimed appear to be due to using small gene samples when individual fluctuations from gene to gene are relatively large.