Selection at the wobble position of codons read by the same tRNA in Saccharomyces cerevisiae

The transfer RNA gene complement of Saccharomyces cerevisiae was utilized f or a whole-genome analysis of the deviation from a neutral usage of pyrimid ine-ending cognate codons, that is, codons read by a single tRNA species ha ving either inosine or guanosine as the first anticodon base. Mutational pr essure at the wobble position was estimated from the base composition of th e noncoding portion of the yeast genome. The selective pressure for transla tional efficiency was inferred from the degree of codon adaptation to tRNA gene redundancy and from mRNA abundance data derived from yeast transcripto me analysis. Amino acid conservation in orthologous comparisons with wholly sequenced microbial genomes was used to estimate translational accuracy re quirements. A close correspondence was observed between the usage of wobble position pyrimidines and the frequency predicted by mutational bias. Howev er, in the case of four cognate pairs (Gly: ggu/ggc; Asn: aau/aac; Phe: uuu /uuc; Tyr: uau/uac) all read by guanosine-starting anticodons, we found evi dence for a strong selective pressure driven by translational efficiency. O nly for the glycine pair, wobble pyrimidine choice also appears to fulfill a translational accuracy requirement. Wobble pyrimidine selection is strict ly related to the number of hydrogen bonds formed by alternative cognate co dons: whenever a different number of hydrogen bonds can be formed at the wo bble position, there is selection against six- or nine-hydrogen-bonded codo n-anticodon pairs. Our results indicate that an intrinsic codon preference, critically dependent on the stability of codon-anticodon interaction and m ainly reflecting selection for the optimization of translational efficiency , is built into the translational apparatus.