Macroevolutionary changes in natural selection on codon usage reflect evolution of the tRNA pool across a budding...

Across taxonomical domains, synonymous codons of an amino acid are found to be used at unequal frequencies within genomes. This codon usage bias (CUB) is highly variable across species. Genome-wide CUB reflects a balance between adaptive and nonadaptive microevolutionary processes within a species. Variation in microevolutionary processes results in across-species variation in CUB. As CUB is tightly linked to important molecular and biophysical processes, it is critical to understand how changes to these processes are linked to changes in microevolutionary processes. We employed a population genetics model to quantify natural selection and mutation biases on a per-codon basis across the Saccharomycotina budding yeast subphylum. We find that the strength of natural selection and mutation biases varied significantly between closely related yeasts. Across-species variation in natural selection reflected the evolution of tRNA gene copy number (tGCN). Additionally, we find that changes to tRNA modification expression can contribute to changes in natural selection across species independent of changes to tGCN. Both lines of evidence support the link between the evolution of the tRNA pool and natural selection in codon usage through changes in the translation efficiency of a codon. Furthermore, we show that changes to tGCN often reflected changes in genome-wide GC%, suggesting changes in the tRNA pool reflect changes in mutation biases. Our work establishes how changes in microevolutionary processes impact changes in molecular mechanisms, ultimately shaping the macroevolutionary variation of a trait.