Pervasive translation in Mycobacterium tuberculosis.
Pervasive translation in Mycobacterium tuberculosis.
复制标题
结核分枝杆菌的普遍翻译。
DOI：
10.7554/elife.73980
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发表时间：
2022-03-28
期刊：
影响因子：
7.7
通讯作者：
Wade, Joseph T.
中科院分区：
文献类型：
--
作者：
Smith, Carol;Canestrari, Jill G.;Wang, Archer J.;Champion, Matthew M.;Derbyshire, Keith M.;Gray, Todd A.;Wade, Joseph T.
大多数细菌开放阅读框都是通过自动预测算法来识别的。然而，这些算法往往无法识别缺乏典型特征的ORF，例如50个密码子的长度或上游Shine-Dalgarno序列的存在。在这里，我们使用核糖体分析方法来识别结核分枝杆菌中主动翻译的ORF。我们发现的大多数ORF以前都没有被描述过，这表明结核分枝杆菌转录组是普遍翻译的。新描述的ORFs主要是短的，许多编码≤50个氨基酸的蛋白质。新发现的ORF的密码子使用情况表明，大多数ORF没有受到纯化选择的影响，因此不太可能对细胞健康做出贡献。然而，我们确定了90个新的ORF(平均长度为52个密码子)，它们具有净化选择的特征。因此，我们的数据表明，结核分枝杆菌中广泛存在的短ORF的翻译为新功能蛋白的进化提供了丰富的来源。你如何预测一个有机体可以制造哪些蛋白质呢？为了回答这个问题，科学家们经常使用计算机程序来扫描物种的遗传信息，以寻找开放阅读框架--一种编码蛋白质的DNA序列。然而，在这些搜索中，非常短的基因和重叠的基因往往会被遗漏。分枝杆菌是一组细菌，其中包括引起结核病的结核分枝杆菌。以前的工作已经预测了数千个结核分枝杆菌的开放阅读框架，但Smith等人。决定使用一种不同的方法来确定是否会有更多。他们专注于核糖体，核糖体是通过阅读相应基因提供的指令来组装特定蛋白质的细胞结构。研究结核分枝杆菌核糖体正在处理的遗传密码片段，发现了数百个新的开放阅读框，其中大多数带有制造非常短蛋白质的指令。更仔细的观察表明，这些蛋白质中只有90种可能在细菌的生命中发挥有用的作用，这可能会为结核病研究打开新的大门。其余的序列没有证据表明已经进化出了有用的工作，但它们仍然是由分枝杆菌制造的。这种无处不在的生产可以通过进化出新的功能蛋白质来帮助细菌适应快速变化的环境。
Most bacterial ORFs are identified by automated prediction algorithms. However, these algorithms often fail to identify ORFs lacking canonical features such as a length of >50 codons or the presence of an upstream Shine-Dalgarno sequence. Here, we use ribosome profiling approaches to identify actively translated ORFs in Mycobacterium tuberculosis. Most of the ORFs we identify have not been previously described, indicating that the M. tuberculosis transcriptome is pervasively translated. The newly described ORFs are predominantly short, with many encoding proteins of ≤50 amino acids. Codon usage of the newly discovered ORFs suggests that most have not been subject to purifying selection, and hence are unlikely to contribute to cell fitness. Nevertheless, we identify 90 new ORFs (median length of 52 codons) that bear the hallmarks of purifying selection. Thus, our data suggest that pervasive translation of short ORFs in Mycobacterium tuberculosis serves as a rich source for the evolution of new functional proteins. How can you predict which proteins an organism can make? To answer this question, scientists often use computer programs that can scan the genetic information of a species for open reading frames – a type of DNA sequence that codes for a protein. However, very short genes and overlapping genes are often missed through these searches. Mycobacteria are a group of bacteria that includes the species Mycobacterium tuberculosis, which causes tuberculosis. Previous work has predicted several thousand open reading frames for M. tuberculosis, but Smith et al. decided to use a different approach to determine whether there could be more. They focused on ribosomes, the cellular structures that assemble a specific protein by reading the instructions provided by the corresponding gene. Examining the sections of genetic code that ribosomes were processing in M. tuberculosis uncovered hundreds of new open reading frames, most of which carried the instructions to make very short proteins. A closer look suggested that only 90 of these proteins were likely to have a useful role in the life of the bacteria, which could open new doors in tuberculosis research. The rest of the sequences showed no evidence of having evolved a useful job, yet they were still manufactured by the mycobacteria. This pervasive production could play a role in helping the bacteria adapt to quickly changing environments by evolving new, functional proteins.