It is well-established that non-random patterns in coding DNA sequence (CDS) features can be partially explained by translational selection. Recent extensions of microarray and proteomic expression data have stimulated many genome-wide investigations of the relationships between gene expression and various CDS features. However, only modest correlations have been found. Here we introduced the one-way ANOVA, a more powerful extension of previous grouping methods, to re-examine these relationships at the whole genome scale for Saccharomyces cerevisiae, where genome-wide protein abundance has been recently quantified. Our results clarify that coding sequence features are inappropriate for use as genome-wide estimators for protein expression levels. This analysis also demonstrates that one-way ANOVA is a powerful and simple method to explore the influence of gene expression on CDS features. (C) 2007 Elsevier Inc. All rights reserved.