Nucleotide polymorphism at the RpII215 gene in Drosophila subobscura: Weakselection on synonymous mutations

Nucleotide variation in an 8.1-kb fragment encompassing the RpII215 gene, w hich encodes the largest subunit of die RNA polymerase II complex, is analy zed in a sample of II chromosomes from a natural population of Drosophila s ubobscura. No amino acid polymorphism was detected among the 157 segregatin g sites. The observed numbers of preferred and unpreferred derived synonymo us mutations can be explained by neutral mutational processes. In contrast, preferred mutations segregate at significantly higher frequency than unpre ferred mutations, suggesting the action of natural selection. The polymorph ism to divergence ratio is different for preferred and unpreferred changes, in agreement with their beneficial and deleterious effects on fitness, res pectively. Preferred and unpreferred codons are nonrandomly distributed in the RpII215 gene:, leading to a heterogeneous distribution of polymorphic t o fixed synonymous differences across this coding region. This intragenic v ariation of the polymorphism/divergence ratio cannot be explained by differ ent patterns of gene expression, mutation, or recombination rates, and ther efore it indicates that selection coefficients for synonymous mutations cal l vary extensively across a coding region. The application of nucleotide co mposition stationarity tests in coding and flanking noncoding regions, assu med to behave neutrally, allows the detection of the action of natural sele ction when stationarity holds in the noncoding region.