ABSTRACT: Genes are often biased in their codon usage. The degree of bias displayed often changes with expression level and intra-genic position. Numerous indices, such as the codon adaptation index, have been developed to measure this bias. While the expression level of a gene and index values are correlated, the heuristic nature of these metrics limits their ability to explain this relationship. As an alternative approach this study integrates mechanistic models of cellular and population processes in a nested manner to develop a stochastic evolutionary model of a protein's production rate.  The model is illustrated using the S. cerevisiae genome and its predictive qualities are compared and contrasted to standard, index based approaches.