Strong Purifying Selection at Synonymous Sites in D. melanogaster

摘要: Synonymous sites are generally assumed to be subject weak selective constraint. For this reason, they often neglected as a possible source of important functional variation. We use site frequency spectra from deep population sequencing data show that, contrary expectation, 22% four-fold synonymous (4D) in Drosophila melanogaster evolve under very strong constraint while few, if any, appear Linking polymorphism with divergence data, we further find that the fraction exposed purifying selection is higher for those positions slower evolution on phylogeny. The function underlying inferred appears separate splicing enhancers, nucleosome positioning, and translational optimization generating canonical codon bias. within gene correlates well expression, particularly mid-late embryo, pupae, adult developmental stages. Genes enriched strongly constrained tend functionally involved key pathways. Given observed widespread acting likely not limited Drosophila, role genetic disease adaptation should reevaluated.