Jossé Lyne, Singh Tarun, von der Haar Tobias
Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, U.K.
Yeast. 2019 Jan;36(1):43-51. doi: 10.1002/yea.3373.
One of the central hypotheses in the theory of codon usage evolution is that in highly expressed genes, particular codon usage patterns arise because they facilitate efficient gene expression and are thus selected for in evolution. Here, we use plasmid copy number assays and growth rate measurements to explore details of the relationship between codon usage, gene expression level, and selective pressure in Saccharomyces cerevisiae. We find that when high expression levels are required, optimal codon usage is beneficial and provides a fitness advantage, consistent with evolutionary theory. However, when high expression levels are not required, optimal codon usage is surprisingly and strongly selected against. We show that this selection acts at the level of protein synthesis, and we exclude a number of molecular mechanisms as the source for this negative selective pressure including nutrient and ribosome limitations and proteotoxicity effects. These findings deepen our understanding of the evolution of codon usage bias, as well as the design of recombinant protein expression systems.
密码子使用进化理论的核心假说之一是，在高表达基因中，特定的密码子使用模式之所以出现，是因为它们有助于高效的基因表达，因此在进化过程中被选择。在这里，我们使用质粒拷贝数测定和生长速率测量来探究酿酒酵母中密码子使用、基因表达水平和选择压力之间关系的细节。我们发现，当需要高表达水平时，最优密码子使用是有益的，并提供了适应性优势，这与进化理论一致。然而，当不需要高表达水平时，最优密码子使用却出人意料地受到强烈的负选择。我们表明这种选择作用于蛋白质合成水平，并且排除了一些分子机制作为这种负选择压力的来源，包括营养和核糖体限制以及蛋白质毒性效应。这些发现加深了我们对密码子使用偏好进化以及重组蛋白表达系统设计的理解。
