University of Hagen, Germany.
BMC Genomics. 2010 Nov 4;11:617. doi: 10.1186/1471-2164-11-617.
In many microbial genomes, a strong preference for a small number of codons can be observed in genes whose products are needed by the cell in large quantities. This codon usage bias (CUB) improves translational accuracy and speed and is one of several factors optimizing cell growth. Whereas CUB and the overrepresentation of individual proteins have been studied in detail, it is still unclear which high-level metabolic categories are subject to translational optimization in different habitats.
In a systematic study of 388 microbial species, we have identified for each genome a specific subset of genes characterized by a marked CUB, which we named the effectome. As expected, gene products related to protein synthesis are abundant in both archaeal and bacterial effectomes. In addition, enzymes contributing to energy production and gene products involved in protein folding and stabilization are overrepresented. The comparison of genomes from eleven habitats shows that the environment has only a minor effect on the composition of the effectomes. As a paradigmatic example, we detailed the effectome content of 37 bacterial genomes that are most likely exposed to strongest selective pressure towards translational optimization. These effectomes accommodate a broad range of protein functions like enzymes related to glycolysis/gluconeogenesis and the TCA cycle, ATP synthases, aminoacyl-tRNA synthetases, chaperones, proteases that degrade misfolded proteins, protectants against oxidative damage, as well as cold shock and outer membrane proteins.
We made clear that effectomes consist of specific subsets of the proteome being involved in several cellular functions. As expected, some functions are related to cell growth and affect speed and quality of protein synthesis. Additionally, the effectomes contain enzymes of central metabolic pathways and cellular functions sustaining microbial life under stress situations. These findings indicate that cell growth is an important but not the only factor modulating translational accuracy and speed by means of CUB.
在许多微生物基因组中,可以观察到细胞大量需要的产物的基因中存在少数密码子的强烈偏好,这种密码子使用偏好(CUB)提高了翻译的准确性和速度,是优化细胞生长的几个因素之一。虽然已经详细研究了 CUB 和个别蛋白质的过表达,但在不同生境中,哪些高级代谢类别受到翻译优化的影响仍不清楚。
在对 388 种微生物物种的系统研究中,我们为每个基因组确定了一组具有明显 CUB 的特定基因子集,我们将其命名为效应组。正如预期的那样,与蛋白质合成相关的基因产物在古菌和细菌效应组中都很丰富。此外,参与能量产生的酶和参与蛋白质折叠和稳定的基因产物也过表达。对来自 11 种生境的基因组的比较表明,环境对效应组的组成只有很小的影响。作为一个典范例子,我们详细说明了 37 个可能受到最强翻译优化选择压力的细菌基因组的效应组内容。这些效应组包含广泛的蛋白质功能,如与糖酵解/糖异生和 TCA 循环、ATP 合酶、氨酰-tRNA 合成酶、伴侣、降解错误折叠蛋白质的蛋白酶、保护免受氧化损伤的保护剂以及冷休克和外膜蛋白相关的酶。
我们清楚地表明,效应组由参与多种细胞功能的蛋白质组的特定子集组成。正如预期的那样,一些功能与细胞生长有关,并影响蛋白质合成的速度和质量。此外,效应组还包含中心代谢途径的酶和维持微生物在应激情况下生存的细胞功能。这些发现表明,细胞生长是调节 CUB 翻译准确性和速度的一个重要但不是唯一的因素。