Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans
Computational and experimental approaches double the number of known introns in the pathogenic yeast Candida albicans
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DOI：
10.1101/gr.6111907
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发表时间：
2007-04-01
期刊：
影响因子：
7
通讯作者：
Johnson, Alexander D.
中科院分区：
文献类型：
--
作者：
Mitrovich, Quinn M.;Tuch, Brian B.;Johnson, Alexander D.
白色念珠菌是人类最常见的真菌病原体。白念珠菌是一种机会性病原体，经常在健康人的消化道内发现，它会在免疫功能低下的人中引起各种临床症状。白念珠菌基因组序列的全面注释最近出版了。由于许多白色念珠菌的编码序列被内含子打断，正确的内含子注释对于准确定义这种病原体中的基因是至关重要的。内含子注释对于识别剪接调控的潜在靶点也很重要，剪接调控是真核生物中一种常见的基因控制机制。在这项研究中，我们报告了一种改进的白色念珠菌内含子注释。除了纠正现有的内含子注释(其中25%是不正确的)外，我们还使用了新的计算和实验方法来识别新的内含子，使总数达到415个，几乎是先前已知数量的两倍。我们的识别方法主要关注内含子特征，而不是蛋白质编码特征，克服了传统内含子注释方法的偏差。内含子在白色念珠菌中并不是随机分布的，而是在参与特定细胞过程的基因中过度表达，如剪接、翻译和线粒体呼吸。这种非随机的分布表明了这些内含子的功能作用，我们证明了内含子具有不寻常序列特征的两个转录本的剪接对环境因素有反应。
Candida albicans is the most common fungal pathogen of humans. Frequently found as a commensal within the digestive tracts of healthy individuals, C. albicans is an opportunistic pathogen that causes a wide variety of clinical syndromes in immuno-compromised individuals. A comprehensive annotation of the C. albicans genome sequence was recently published. Because many C. albicans coding sequences are interrupted by introns, proper intron annotation is essential for the accurate definition of genes in this pathogen. Intron annotation is also important for identifying potential targets of splicing regulation, a common mechanism of gene control in eukaryotes. In this study, we report an improved annotation of C. albicans introns. In addition to correcting the existing intron annotations, 25% of which were incorrect, we have used novel computational and experimental approaches to identify new introns, bringing the total to 415, almost double the number previously known. Our identification methods focus primarily on intron features rather than protein-coding features, overcoming biases of traditional intron annotation methods. Introns are not randomly distributed in C. albicans, and are over-represented in genes involved in specific cellular processes, such as splicing, translation, and mitochondrial respiration. This nonrandom distribution suggests functional roles for these introns, and we demonstrate that splicing of two transcripts whose introns have unusual sequence features is responsive to environmental factors.