Beyond Codon Usage Bias: The Regulation of Translation Encoded in Synonymous Sites. David S. Lawrie¹, Dmitri A. Petrov². 1) Genetics, Stanford University, Stanford, CA; 2) Biology, Stanford University, Stanford, CA.

   Using the signature of selective constraint from polymorphism data in the synonymous sites of D. melanogaster, we identify synonymous codons favored by strong purifying selection. While these favored codons often overlap with optimal codons as defined by canonical codon bias, non-optimal codons can be under greater selective constraint. Meanwhile, those codons rarely used in the D. melanogaster genome appear to be evolving neutrally. Evolutionary analysis over the Drosophila phylogeny supports the existence of at least two selective forces operating on synonymous sites: one force, a weak force, drives the signature of codon bias and preferentially conserves optimal codons; a second selective force, a strong force, favors both optimal and non-optimal codons. This strong constraint is enriched in highly expressed genes, particularly so in genes expressed in mid-late embryonic, pupal, and adult stages of development. We plan to further investigate the signal of constraint in the context of riboprofiling data detailing translationally fast and slow sites.