Silov Serhii, Zaburannyi Nestor, Anisimova Maria, Ostash Bohdan
Department of Genetics and Biotechnology, Ivan Franko National University of Lviv, Hrushevskoho Str. 4, Lviv, 79005 Ukraine.
Institute of Applied Simulations, School of Life Sciences and Facility Management, Zürich University of Applied Sciences, Einsiedlerstrasse 31a, 8820 Wädenswil, Switzerland.
Indian J Microbiol. 2021 Mar;61(1):24-30. doi: 10.1007/s12088-020-00902-6. Epub 2020 Jul 31.
Streptomycetes, Gram-positive bacteria with huge and GC-rich genomes provide an ample example of codon usage bias taken to the extreme. Particularly, in all sequenced to date streptomycete genomes leucyl codon TTA is the rarest one. It is present (usually once or twice) in 70-200 out of 7000-8000 coding sequences that make up a typical streptomycete genome. tRNA of streptomycetes, encoded by the gene, has been shown to be present in mature form only after the onset of morphological differentiation and activation of secondary metabolism. Consequently, during the early stages of cell growth, the translation of genes carrying the TTA codon can be interrupted due to the absence of tRNA . Several reports show that mutations of TTA to synonymous codons in certain genes indeed relieve their expression from dependence. However, the deletion of does not always arrest the expression of TTA-containing genes. The nucleotides T/C downstream of TTA were suggested, in 2002, to favor TTA mistranslation. We tested this hypothesis using sizable datasets derived from individual genome and a subset of TTA+ genes for secondary metabolism known for their active expression. Our results revealed nucleotide biases downstream of NNA codons family, such as the preference for C and the avoidance of A. Yet, none of the observed biases was sufficient to claim a special case for TTA codon. Hence, the issue of codon context and TTA codon mistranslation in deserves further elaboration.
链霉菌是革兰氏阳性细菌，具有庞大且富含GC的基因组，是密码子使用偏好走向极端的一个典型例子。特别是，在迄今为止所有已测序的链霉菌基因组中，亮氨酰密码子TTA是最罕见的。在构成典型链霉菌基因组的7000 - 8000个编码序列中，它存在于（通常一到两次）70 - 200个序列中。由该基因编码的链霉菌tRNA已被证明仅在形态分化开始和次级代谢激活后才以成熟形式存在。因此，在细胞生长的早期阶段，携带TTA密码子的基因的翻译可能会因缺乏tRNA而中断。一些报告表明，某些基因中TTA突变为同义密码子确实能使其表达摆脱对tRNA的依赖。然而，删除该基因并不总是会阻止含TTA基因的表达。2002年有人提出，TTA下游的核苷酸T/C有利于TTA错译。我们使用来自单个链霉菌基因组和一组已知活跃表达的次级代谢TTA +基因的大量数据集对这一假设进行了测试。我们的结果揭示了NNA密码子家族下游的核苷酸偏好，例如对C的偏好和对A的回避。然而，观察到的偏差都不足以说明TTA密码子是一个特殊情况。因此，链霉菌中密码子上下文和TTA密码子错译的问题值得进一步阐述。
