Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva
Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva
复制标题
DOI：
10.1186/1471-2164-9-582
复制
发表时间：
2008-12-03
期刊：
影响因子：
4.4
通讯作者：
Silva, Joana C.
中科院分区：
文献类型：
--
作者：
Guo, Xiang;Silva, Joana C.
背景：牛肠杆菌属寄生虫引起牛淋巴细胞增生性疾病，造成巨大的社会经济损失。细小T.和环状T.的基因组序列和注释的可用性为研究寄生虫生物学及其与宿主细胞转化和趋向性的关系提供了便利。然而，这一属的转录调控机制，这可能是了解其寄生学基本方面的关键，仍然知之甚少。在这项研究中，我们分析了他们基因组中非编码序列的进化，并确定了可能参与这些寄生物种基因调控的保守序列元件。结果：喜勒菌的基因间区和内含子较短，长度分布呈明显的右偏。5′-5′方向基因的基因间区比两个终止密码子的基因间区更长，且at含量略高；3′-5′取向基因两侧的基因间区长度和AT组成均为中等值。内含子位置与内含子长度负相关，与GC含量正相关。利用严格的标准，我们鉴定出了一组高质量的parva和T. annulata之间的同源非编码序列，并确定了跨区域的选择约束分布，表明在翻译起始位点附近的选择约束更高。基因间区和内含子的约束与长度呈正相关，表明非编码区长度扩展受到严格控制。对功能元件的全基因组搜索揭示了他们基因组基因间区域的几个保守基序。两个这样的基序优先位于T. parva转录起始位点上游的前60个碱基对内，优先与特定的蛋白质功能类别相关，并且与其他物种中的已知调控基序具有显著的相似性。这些结果表明，这两个基序可能代表了他们的转录因子结合位点。结论：他们的基因组高度紧凑，选择似乎倾向于短内含子和基因间区域。在两种芽孢杆菌的基因间区独立鉴定了三个代表性过强的序列基序，证据表明其中至少有两个在小孢子虫的转录控制中起作用。这些是在这种单细胞真核寄生虫中转录因子结合位点实验验证的主要候选者。在疟原虫中，与这两种梭菌基序相似的序列是保守的，这暗示了在顶复合体门中可能存在共同的调节机制。
Background: Parasites in the genus Theileria cause lymphoproliferative diseases in cattle, resulting in enormous socio-economic losses. The availability of the genome sequences and annotation for T. parva and T. annulata has facilitated the study of parasite biology and their relationship with host cell transformation and tropism. However, the mechanism of transcriptional regulation in this genus, which may be key to understanding fundamental aspects of its parasitology, remains poorly understood. In this study, we analyze the evolution of non-coding sequences in the Theileria genome and identify conserved sequence elements that may be involved in gene regulation of these parasitic species.Results: Intergenic regions and introns in Theileria are short, and their length distributions are considerably right-skewed. Intergenic regions flanked by genes in 5'-5' orientation tend to be longer and slightly more AT-rich than those flanked by two stop codons; intergenic regions flanked by genes in 3'-5' orientation have intermediate values of length and AT composition. Intron position is negatively correlated with intron length, and positively correlated with GC content. Using stringent criteria, we identified a set of high-quality orthologous non-coding sequences between T. parva and T. annulata, and determined the distribution of selective constraints across regions, which are shown to be higher close to translation start sites. A positive correlation between constraint and length in both intergenic regions and introns suggests a tight control over length expansion of non-coding regions. Genome-wide searches for functional elements revealed several conserved motifs in intergenic regions of Theileria genomes. Two such motifs are preferentially located within the first 60 base pairs upstream of transcription start sites in T. parva, are preferentially associated with specific protein functional categories, and have significant similarity to know regulatory motifs in other species. These results suggest that these two motifs are likely to represent transcription factor binding sites in Theileria.Conclusion: Theileria genomes are highly compact, with selection seemingly favoring short introns and intergenic regions. Three over-represented sequence motifs were independently identified in intergenic regions of both Theileria species, and the evidence suggests that at least two of them play a role in transcriptional control in T. parva. These are prime candidates for experimental validation of transcription factor binding sites in this single-celled eukaryotic parasite. Sequences similar to two of these Theileria motifs are conserved in Plasmodium hinting at the possibility of common regulatory machinery across the phylum Apicomplexa.