Variation in the Pattern of Synonymous and Nonsynonymous Difference Between Two Fungal Genomes

Abstract

The proportion of synonymous nucleotide differences per synonymous site (p_S) and the proportion of nonsynonymous differences per nonsynonymous site (p_N) were computed at 1,993,217 individual codons in 4,133 protein-coding genes between the two yeast species Saccharomyces cerevisiae and Saccharomyces paradoxus. When the modified Nei-Gojobori method was used, significantly more codons with p_N > p_S were observed than expected, based on random pairing of observed p_S and p_N values. However, this finding was most likely explained by the presence of a strong negative correlation between the number of synonymous differences and the number of nonsynonymous differences at codons with at least one difference. As a result of this correlation, codons with p_N > p_S were characterized not only by unusually high p_N but also by unusually low p_S. On the other hand, the number of codons with (where p_S is the mean for all codons) was very similar to the random expectation, and the observed number of 30-codon windows with p_N > p_S was significantly lower than the random expectation. These results imply that the occurrence of a certain number of codons or codon windows with p_N > p_S is expected given the nature of nucleotide substitution and need not imply the action of positive Darwinian selection.