Transcription profiling reveals stage- and function-dependent expression patterns in the filarial nematode Brugia malayi.
Transcription profiling reveals stage- and function-dependent expression patterns in the filarial nematode Brugia malayi.
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DOI：
10.1186/1471-2164-13-184
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发表时间：
2012-05-14
期刊：
影响因子：
4.4
通讯作者：
Weil GJ
中科院分区：
文献类型：
--
作者：
Li BW;Wang Z;Rush AC;Mitreva M;Weil GJ
马来丝虫是一种线虫寄生虫，会导致淋巴丝虫病，这是一种毁容和令人不适的热带疾病。尽管2007年公布了第一批基因组序列草案，但人们对控制寄生虫发育和在哺乳动物和昆虫宿主中生存所需的发育变化的转录程序知之甚少。我们使用带有代表约85%预测基因的探针的微阵列来生成七个寄生虫生命周期阶段/性别的基因表达谱。在具有可检测到的表达信号的转录本中，大约41%的转录本在不同的生命周期阶段存在差异表达。26%的转录本仅在单个寄生虫阶段表达，27%在所研究的所有阶段表达。对差异表达的转录本进行K-Means聚类，发现了与寄生虫生命周期阶段或性别相关的五种主要转录模式。对已知的阶段相关转录本的检查证实了这些数据集，并表明新确定的阶段或性别相关转录本可能在发育和生殖中行使生物学功能。结果还表明，具有相似转录模式的基因通常参与相似的功能或细胞过程。例如，核受体家族基因转录在基因表达模式4(雌性丰富)中上调，而蛋白激酶基因家族转录在表达模式5(男性丰富)中上调。我们还使用配对比较来确定生命周期阶段和性别之间的转录变化。对马来丝虫生命周期基因表达模式的分析为丝虫生物学提供了新的见解。由阶段相关和/或阶段特定转录本编码的蛋白质对于寄生虫的关键功能可能是至关重要的，例如建立和维持感染、发育、繁殖和在宿主中的生存。其中一些可能是丝虫病疫苗或新药治疗的有用靶点。
Brugia malayi is a nematode parasite that causes lymphatic filariasis, a disfiguring and disabiling tropical disease. Although a first draft genome sequence was released in 2007, very little is understood about transcription programs that govern developmental changes required for the parasite’s development and survival in its mammalian and insect hosts. We used a microarray with probes that represent some 85% of predicted genes to generate gene expression profiles for seven parasite life cycle stages/sexes. Approximately 41% of transcripts with detectable expression signals were differentially expressed across lifecycle stages. Twenty-six percent of transcripts were exclusively expressed in a single parasite stage, and 27% were expressed in all stages studied. K-means clustering of differentially expressed transcripts revealed five major transcription patterns that were associated with parasite lifecycle stages or gender. Examination of known stage-associated transcripts validated these data sets and suggested that newly identified stage or gender-associated transcripts may exercise biological functions in development and reproduction. The results also indicate that genes with similar transcription patterns were often involved in similar functions or cellular processes. For example, nuclear receptor family gene transcripts were upregulated in gene expression pattern four (female-enriched) while protein kinase gene family transcripts were upregulated in expression pattern five (male-enriched). We also used pair-wise comparisons to identify transcriptional changes between life cycle stages and sexes. Analysis of gene expression patterns of lifecycle in B. malayi has provided novel insights into the biology of filarial parasites. Proteins encoded by stage-associated and/or stage-specific transcripts are likely to be critically important for key parasite functions such as establishment and maintenance of infection, development, reproduction, and survival in the host. Some of these may be useful targets for vaccines or new drug treatments for filariasis.