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Why does a cell produce a particular amount of protein? Why does a protein-coding sequence use a particular set of nucleotides? These questions are central to understanding the evolution of the proteome across species. Here, I will present work on two key aspects of proteome evolution using models that decompose the influences of mutation and natural selection to address these questions. First, the non-uniform usage of synonymous codons, or codon usage bias (CUB), is a universal feature of genomes, but varies in direction and magnitude across species. Using a population genetics model assuming selection-mutation-drift equilibrium, we quantified CUB across 327 budding yeast species. We linked variation in natural selection on synonymous codon usage with changes to the tRNA pool, consistent with selection for efficient translation. Furthermore, we find evidence that changes to the tRNA pool reflect changes in genome-wide nucleotide content. This suggests a model in which mutation bias shapes the selectively favored synonym via the tRNA pool, a key factor determining codon-specific translation efficiency. Second, changes to gene expression are a major driver of phenotypic variation across species. Gene expression results from multiple processes, from transcription through post-translational regulation, requiring evolutionary models that capture their mechanistic relationships. The regulation of mRNA and protein abundances is well studied, but less is known about the evolutionary processes that shape their relationship. We derived a new phylogenetic model and applied it to mRNA and protein abundance data across ten mammalian species. Our analyses reveal strong stabilizing selection on protein abundances over macroevolutionary time, that mutations affecting mRNA abundance minimally affect protein abundance, that mRNA abundances evolve under selection to track protein abundances, and that mRNA abundances adapt faster than protein abundances due to greater mutational opportunity. Together, these projects show how decomposing mutation and selection can reveal the evolutionary rules governing the proteome, from codon choice to the coevolution of gene expression.