Diversity of preferred nucleotide sequences around the translation initiation codon in eukaryote genomes.

Diversity of preferred nucleotide sequences around the translation initiation codon in eukaryote genomes.
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DOI:
10.1093/nar/gkm1102
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发表时间:
2008-02
影响因子:
14.9
通讯作者:
Miura K
Miura K
中科院分区:
生物学2区
文献类型:
--
作者:
Nakagawa S;Niimura Y;Gojobori T;Tanaka H;Miura K

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了解真核生物中蛋白质合成的调控机制对于基因组序列的准确注释至关重要。Kozak报告说,核苷酸序列GCCGCC(A/G)CXCGG(AUG是起始密码子)经常在脊椎动物基因中观察到,并且该“共有”序列增强翻译起始。然而,后来使用无脊椎动物,真菌和植物基因的研究报告了不同的“共有”序列。在这项研究中,我们进行了广泛的比较分析的核苷酸序列的起始密码子周围的基因组数据,从47个真核生物物种,包括动物,真菌,植物和原生生物。分析表明,偏好的核苷酸序列在不同物种之间是相当不同的,但核苷酸偏好模式之间的差异大致反映了物种的进化关系。我们还发现了在位置-3处的A/G,位置-2处的A/C和位置+5处的C的强烈偏倚,这在所有检查的物种中都是常见的。具有较高表达水平的基因显示出较强的信号,表明这些核苷酸负责调节翻译起始。起始密码子周围的优选核苷酸序列的多样性可能是由两种不同模式GCCGCCAUG和AAAAAAAUG的相对贡献的差异来解释的,这意味着存在多种控制翻译起始的分子机制。
Understanding regulatory mechanisms of protein synthesis in eukaryotes is essential for the accurate annotation of genome sequences. Kozak reported that the nucleotide sequence GCCGCC(A/G)CCAUGG (AUG is the initiation codon) was frequently observed in vertebrate genes and that this ‘consensus’ sequence enhanced translation initiation. However, later studies using invertebrate, fungal and plant genes reported different ‘consensus’ sequences. In this study, we conducted extensive comparative analyses of nucleotide sequences around the initiation codon by using genomic data from 47 eukaryote species including animals, fungi, plants and protists. The analyses revealed that preferred nucleotide sequences are quite diverse among different species, but differences between patterns of nucleotide bias roughly reflect the evolutionary relationships of the species. We also found strong biases of A/G at position −3, A/C at position −2 and C at position +5 that were commonly observed in all species examined. Genes with higher expression levels showed stronger signals, suggesting that these nucleotides are responsible for the regulation of translation initiation. The diversity of preferred nucleotide sequences around the initiation codon might be explained by differences in relative contributions from two distinct patterns, GCCGCCAUG and AAAAAAAUG, which implies the presence of multiple molecular mechanisms for controlling translation initiation.
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