THE CORRELATION BETWEEN SYNONYMOUS AND NONSYNONYMOUS SUBSTITUTIONS INDROSOPHILA - MUTATION, SELECTION OR RELAXED CONSTRAINTS

Codon usage bias, the preferential use of particular codons within eac h codon family, is characteristic of synonymous base composition in ma ny species, including Drosophila, yeast, and many bacteria. Preferenti al usage of particular codons in these species is maintained by natura l selection acting largely at the level of translation. In Drosophila, as in bacteria, the rate of synonymous substitution per site is negat ively correlated with the degree of codon usage bias, indicating stron ger selection on codon usage in genes with high codon bias than in gen es with low codon bias. Surprisingly, in these organisms, as well as i n mammals, the rate of synonymous substitution is also positively corr elated with the rate of nonsynonymous substitution. To investigate thi s correlation, we carried out a phylogenetic analysis of substitutions in 22 genes between two species of Drosophila, Drosophila pseudoobscu ra and D. subobscura, in codons that differ by one replacement and one synonymous change. We provide evidence for a relative excess of doubl e substitutions in the same species lineage that cannot be explained b y the simultaneous mutation of two adjacent bases. The synonymous chan ges in these codons also cannot be explained by a shift to a more pref erred codon following a replacement substitution. We, therefore, inter pret the excess of double codon substitutions within a lineage as bein g the result of relaxed constraints on both kinds of substitutions in particular codons.