Cope Alexander L, Shah Premal
Department of Genetics, Rutgers University, Piscataway, NJ 08854.
Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903.
Proc Natl Acad Sci U S A. 2025 Jul 8;122(27):e2419889122. doi: 10.1073/pnas.2419889122. Epub 2025 Jul 1.
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.
在不同的分类领域中，人们发现氨基酸的同义密码子在基因组内的使用频率并不相等。这种密码子使用偏好（CUB）在不同物种间差异很大。全基因组的CUB反映了一个物种内适应性和非适应性微观进化过程之间的平衡。微观进化过程的变化导致了CUB在物种间的差异。由于CUB与重要的分子和生物物理过程紧密相关，了解这些过程的变化如何与微观进化过程的变化相联系至关重要。我们采用了一种群体遗传学模型，以逐个密码子为基础，量化了子囊菌酵母亚门中酿酒酵母的自然选择和突变偏好。我们发现，亲缘关系相近的酵母之间，自然选择和突变偏好的强度差异显著。自然选择的物种间差异反映了tRNA基因拷贝数（tGCN）的进化。此外，我们发现tRNA修饰表达的变化可以独立于tGCN的变化，导致物种间自然选择的变化。这两条证据都支持了tRNA库的进化与密码子使用中的自然选择之间，通过密码子翻译效率的变化建立的联系。此外，我们还表明，tGCN的变化通常反映了全基因组GC%的变化，这表明tRNA库的变化反映了突变偏好的变化。我们的工作确立了微观进化过程的变化如何影响分子机制的变化，最终塑造了一个性状的宏观进化变异。
