Zavala Bryan, Dineen Lauren, Fisher Kaitlin J, Opulente Dana A, Harrison Marie-Claire, Wolters John F, Shen Xing-Xing, Zhou Xiaofan, Groenewald Marizeth, Hittinger Chris Todd, Rokas Antonis, LaBella Abigail Leavitt
bioRxiv. 2024 May 24:2024.05.23.595506. doi: 10.1101/2024.05.23.595506.
Codon usage bias, or the unequal use of synonymous codons, is observed across genes, genomes, and between species. The biased use of synonymous codons has been implicated in many cellular functions, such as translation dynamics and transcript stability, but can also be shaped by neutral forces. The Saccharomycotina, the fungal subphylum containing the yeasts and , has been a model system for studying codon usage. We characterized codon usage across 1,154 strains from 1,051 species to gain insight into the biases, molecular mechanisms, evolution, and genomic features contributing to codon usage patterns across the subphylum. We found evidence of a general preference for A/T-ending codons and correlations between codon usage bias, GC content, and tRNA-ome size. Codon usage bias is also distinct between the 12 orders within the subphylum to such a degree that yeasts can be classified into orders with an accuracy greater than 90% using a machine learning algorithm trained on codon usage. We also characterized the degree to which codon usage bias is impacted by translational selection. Interestingly, the degree of translational selection was influenced by a combination of genome features and assembly metrics that included the number of coding sequences, BUSCO count, and genome length. Our analysis also revealed an extreme bias in codon usage in the Saccharomycodales associated with a lack of predicted arginine tRNAs. The order contains 24 species, and 23 are computationally predicted to lack tRNAs that decode CGN codons, leaving only the AGN codons to encode arginine. Analysis of Saccharomycodales gene expression, tRNA sequences, and codon evolution suggests that extreme avoidance of the CGN codons is associated with a decline in arginine tRNA function. Codon usage bias within the Saccharomycotina is generally consistent with previous investigations in fungi, which show a role for both genomic features and GC bias in shaping codon usage. However, we find cases of extreme codon usage preference and avoidance along yeast lineages, suggesting additional forces may be shaping the evolution of specific codons.
密码子使用偏好，即同义密码子的不均衡使用，在基因、基因组以及物种之间均有体现。同义密码子的偏向性使用与许多细胞功能相关，如翻译动力学和转录稳定性，但也可能受到中性力量的影响。子囊菌纲酵母亚门包含酵母等真菌，一直是研究密码子使用的模式系统。我们对来自1051个物种的1154个菌株的密码子使用情况进行了表征，以深入了解导致该亚门密码子使用模式的偏好、分子机制、进化及基因组特征。我们发现了对以A/T结尾密码子的普遍偏好，以及密码子使用偏好、GC含量和tRNA组大小之间的相关性。该亚门内的12个目之间的密码子使用偏好也存在显著差异，以至于使用基于密码子使用情况训练的机器学习算法，酵母可以以超过90%的准确率被分类到各个目中。我们还表征了翻译选择对密码子使用偏好的影响程度。有趣的是，翻译选择的程度受到基因组特征和组装指标的综合影响，这些指标包括编码序列的数量、BUSCO计数和基因组长度。我们的分析还揭示了酵母目密码子使用的极端偏向性，这与预测的精氨酸tRNA的缺乏有关。该目包含24个物种，经计算预测其中23个物种缺乏解码CGN密码子的tRNA，仅剩下AGN密码子来编码精氨酸。对酵母目基因表达、tRNA序列和密码子进化的分析表明，对CGN密码子的极端回避与精氨酸tRNA功能的下降有关。子囊菌纲内的密码子使用偏好总体上与先前对真菌的研究一致，这些研究表明基因组特征和GC偏向在塑造密码子使用方面都发挥了作用。然而，我们发现酵母谱系中存在极端密码子使用偏好和回避的情况，这表明可能有其他力量在塑造特定密码子的进化。
