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^Leu_UAA of streptomycetes, encoded by the bldA 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^Leu_UAA. Several reports show that mutations of TTA to synonymous codons in certain genes indeed relieve their expression from bldA dependence. However, the deletion of bldA 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 Streptomyces 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 Streptomyces deserves further elaboration.

链霉菌，革兰氏阳性细菌具有巨大且富含 GC 的基因组，提供了一个极端的密码子使用偏差的充分例子。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 是最稀有的。它存在于构成典型链霉菌基因组的 7000-8000 个编码序列中的 70-200 个中（通常是一次或两次）。链霉菌的tRNA ^Leu _UAA由bldA基因编码，仅在形态分化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由于 tRNA ^Leu _{UAA的缺失而中断}. 一些报告表明，某些基因中 TTA 突变为同义密码子确实减轻了它们对bldA依赖性的表达。然而，bldA的缺失并不总是阻止含有 TTA 的基因的表达。2002 年，有人建议 TTA 下游的核苷酸 T/C 有利于 TTA 误译。我们使用来自单个链霉菌的大量数据集测试了这一假设基因组和一个以活跃表达而闻名的二次代谢的 TTA+ 基因子集。我们的结果揭示了 NNA 密码子家族下游的核苷酸偏差，例如对 C 的偏好和对 A 的避免。然而，观察到的偏差都不足以证明 TTA 密码子的特殊情况。因此，链霉菌中的密码子上下文和 TTA 密码子误译问题值得进一步阐述。