分泌蛋白基因编码区5’端密码子使用偏好性研究

发布时间：2018-06-21 11:41

本文选题：密码子偏好性 + 稀有密码子　；参考：《西北农林科技大学》2016年硕士论文

【摘要】：密码子使用偏好性现象普遍存在于基因组之间和基因组内部。在细菌中密码子偏好性和基因组的核苷酸组成密切相关,但真核生物中这种相关性并不强。密码子偏好性影响翻译调控的多个阶段。一般将基因组使用频率较高的密码子称为通用密码子,反之为稀有密码子。研究表明,稀有密码子在蛋白质编码区(CDS,Coding sequence)5’端使用更多,可帮助调控早期翻译速率和协助共翻译过程。此外,稀有密码子在不同基因中的分布规律也很不相同。分泌蛋白是细胞中一大类特殊的蛋白,其CDS 5’末端编码信号肽序列,引导蛋白质定位到真核生物的内质网膜或原核生物的细胞膜。信号肽区域及其下游区域都存在稀有密码子的聚集。稀有密码子在分泌蛋白基因编码区5’端除了调控翻译速度以外,可能存在更加复杂的生物学功能。目前关于分泌蛋白基因的密码子偏好性研究主要集中在末端信号肽区域,而较少涉及下游区域。同时除了大肠杆菌和酿酒酵母,缺少对其他物种中分泌蛋白基因密码子偏好性的全面研究。本论文在六个真核物种(黑腹果蝇、秀丽隐杆线虫、小鼠、人类、拟南芥和酿酒酵母)中研究了具有信号肽序列的分泌蛋白基因中的密码子使用偏好性。结果发现,分泌蛋白基因在编码区5’端的稀有密码子使用频率比非分泌蛋白基因5’端更高。对编码区5’端稀有密码子聚集区域的分析表明,分泌蛋白基因的稀有密码子存在两个不同的聚集区域,起始密码下游前20个密码子和第75 100个密码子。在不同区域内出现稀有密码子聚集的分泌蛋白基因参与不同的生理过程。分泌蛋白基因编码区5’端的稀有密码子偏好性部分来自于信号肽疏水区域的氨基酸偏好性影响。虽然分泌蛋白基因更容易在某些区域出现稀有密码子的聚集,但稀有密码子串联出现的情况依然少有发生。我们认为翻译早期过多的连续稀有密码子出现会增加核糖体碰撞、掉落事件发生的可能性,严重阻碍翻译延伸的正常进行。因此,连续稀有密码子并不会频繁出现。核糖体密度数据分析结果发现稀有密码子和通用密码子的平均翻译速率没有显著差异。不过分泌蛋白基因中存在两个容易出现核糖体强停顿的区域。一个是起始密码子附近,另一个是起始密码子下游20 30个密码子区域,两个区域的核糖体停顿可能具有不同的调控功能。综上,分泌蛋白基因编码区5’端偏好使用稀有密码子,具有不同生物学功能的基因倾向于在不同的局部区域出现稀有密码子聚集,然而又不会选择在相邻位置频繁使用稀有密码子;同时稀有密码子的翻译速度并没有显著地低于通用密码子。本论文的结果进一步揭示了真核生物分泌蛋白基因中的密码子使用规律,为今后研究稀有密码子和其他翻译调控因素如mRNA二级结构、tRNA丰度等的协同作用提供了理论支持。
[Abstract]:Codon usage preference is common between genomes and within genomes. Codon preference in bacteria is closely related to nucleotide composition in the genome, but not in eukaryotes. Codon preference affects multiple stages of translation regulation. The codon with high frequency is generally referred to as the common codon, whereas the other is rare codon. It has been shown that the rare codon is used more frequently at the 5 'end of the protein coding region, which can help to regulate the early translation rate and assist in the co-translation process. In addition, the distribution of rare codon in different genes is also very different. Secretory protein is a kind of special protein in cell. Its CDS 5'terminal coding signal peptide sequence directs the protein to locate to the endoplasmic omentum of eukaryote or the cell membrane of prokaryote. There are rare codon aggregation in the signal peptide region and its downstream region. In addition to regulating translation speed, rare codon may have more complex biological functions at the 5 'end of secretory protein gene coding region. At present, the codon preference of secretory protein gene is mainly focused on the terminal signal peptide region, but less on the downstream region. Besides Escherichia coli and Saccharomyces cerevisiae, there is no comprehensive study on the codon preference of secretory protein gene in other species. The codon usage preference of secretory protein genes with signal peptide sequences was studied in six eukaryotic species (Drosophila melanogaster, Cryptotella elegans, mouse, human, Arabidopsis thaliana and Saccharomyces cerevisiae). The results showed that the rare codon of secretory protein gene at the 5 'end of the coding region was higher than that at the 5' end of the non secretory protein gene. The analysis of the 5 '-terminal rare codon cluster region showed that there were two different clustering regions in the rare codon of secretory protein gene: the first 20 codon downstream of the initial codon and the 75th 100 codon. The secretory protein genes with rare codon aggregation in different regions are involved in different physiological processes. The rare codon preference at the 5 'end of secretory protein gene is partly due to the amino acid preference in the hydrophobic region of the signal peptide. Although secretory protein genes are more likely to have rarity codon aggregation in some regions, rare codon concatenation is still rare. We think that the occurrence of excessive continuous rare codon in early translation will increase the possibility of ribosomal collision and fall, and seriously hinder the normal process of translation extension. Therefore, continuous rare codon does not occur frequently. The analysis of ribosomal density data showed that there was no significant difference between the average translation rates of rare codon and common codon. However, there are two regions of the secretory protein gene that are prone to strong ribosomal pauses. One is near the start codon and the other is the 20 ~ (30) codon downstream of the start codon. Ribosomal pauses in both regions may have different regulatory functions. In conclusion, the 5 'end of secretory protein gene coding region prefers to use rare codon, and genes with different biological functions tend to cluster rare codon in different local regions. However, the rare codon is not used frequently in the adjacent position, and the translation speed of the rare codon is not significantly lower than that of the common codon. The results of this paper further reveal the rule of codon use in eukaryotic secretory protein gene and provide theoretical support for the further study of the synergism of rare codon and other translation regulatory factors such as mRNA secondary structure tRNA abundance.
【学位授予单位】：西北农林科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：Q78

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