Synonymous rates at the RpII215 gene of Drosophila: Variation among species and across the coding region

The region encompassing the RpII215 gene that encodes the largest component of the RNA polymerase II complex (1889 amino acids) has been sequenced in Drosophila subobscura, D. madeirensis, D. guanche, and D. pseudoobscura. No nsynonymous divergence estimates (K-a) indicate that this gene has a very l ow rate of amino acid replacements. Given its low K-a and constitutive expr ession, synonymous substitution rates are, however, unexpectedly high. Sequ ence comparisons have allowed the molecular clock hypothesis to be tested. D. guanche is an insular species and it is therefore expected to have a red uced effective size relative to D. subobscura. The significantly higher rat e of synonymous substitutions detected in the D. guanche lineage could be e xplained if synonymous mutations behave as nearly neutral. Significant depa rture from the molecular clock hypothesis for synonymous and nonsynonymous substitutions was detected when comparing the D. subobscura, D. pseudoobscu ra, and D. melanogaster lineages. Codon bias and synonymous divergence betw een D. subobscura and D. melanogaster were negatively correlated across the RpII215 coding region, which indicates that selection coefficients for syn onymous mutations vary across the gene. The C-terminal domain (CTD) of the RpII215 protein is structurally and functionally differentiated from the re st of the protein. Synonymous substitution rates were significantly differe nt in both regions, which strongly indicates that synonymous mutations in t he CTD and in the non-CTD regions are under detectably different selection coefficients.