Bacteria-like information processing in ancestral mitochondria

线粒体是如何产生的 线粒体是所有真核生物(包括人类、真菌、植物和各种原生动物/原生生物)细胞内的一种器官样结构(细胞器)。虽然线粒体通常被称为细胞的动力源，但它也扮演着重要的新陈代谢角色：它们为整个细胞提供各种构件(碳水化合物、氨基酸、核苷酸、脂肪酸和铁硫化合物)。我们现在知道线粒体拥有自己的基因组和特殊的机制，用于细胞器分裂、DNA复制、将基因转录成信使RNA，以及将信使RNA翻译成蛋白质(细胞膜和酶的制造材料)。线粒体的这种半自主性是它们祖先的遗迹：它们起源于大约10亿年前栖息在真核细胞中的内共生细菌。 在从共生细菌到细胞器的初始过渡阶段，原始线粒体基因组必须编码1000多个指定线粒体蛋白质的基因，并在基因组组织、RNA转录和蛋白质翻译方面遵守细菌的惯例。然而，在动物、真菌和植物的今天的线粒体中，基因组织和基因表达几乎没有它们过去细菌的痕迹。 我们的研究计划旨在阐明内共生细菌祖先的“驯化”所涉及的步骤，并追踪线粒体的前身转化为真核细胞器的过程。通过我们在单细胞、有鞭毛的原生动物中发现了与细菌基因组相似的微型线粒体DNA，这些问题现在可以有效地得到解决。在我们计划的前五年，我们建议调查线粒体信息处理，从基因到RNA再到蛋白质，在多大程度上类似于细菌，或者更确切地说，像我们所知的来自动物、真菌和植物的“现代”线粒体。我们的方法将结合经典生物化学、新一代基因组学方法论和生物信息学，为各级学生提供充足的多学科培训机会。

HOW MITOCHONDRIA CAME ABOUT Mitochondria are an organ-like structure (organelle) within the cells of all eukaryotes (animals including humans, fungi, plants, and the large and diverse assemblage of protozoans/protists). While usually referred to as the cell's powerhouse, mitochondria play also an import metabolic role: they supply the entire cell with various building blocks (carbohydrates, amino acids, nucleotides, fatty acids, and iron-sulfur compounds). We now know that mitochondria possess their own genome and particular machineries for organelle division, DNA replication, transcription of genes into messenger RNAs, and translation of messenger RNAs into proteins (the material from which cellular membranes and enzymes are made). This semi-autonomy of mitochondria is a vestige of their ancestry: they originate from endosymbiotic bacteria that took up residence in the eukaryotic cell about a billion years ago. In the initial transition phase from a symbiotic bacterium to an organelle, the proto-mitochondrial genome must have encoded more than a thousand genes specifying mitochondrial proteins, and adhered to bacterial conventions with respect to genome organization, RNA transcription and protein translation. However, in present-day mitochondria from animals, fungi and plants, gene organization and gene expression bear little traces of their bacterial past. Our research program aims at elucidating the steps that were involved in the 'domestication' of the endosymbiotic bacterial ancestor, and tracing the processes by which the predecessor of mitochondria was transformed into a eukaryotic organelle. These questions can now be tackled effectively through our discovery --in unicellular, flagellated protozoans called jakobids-- of mitochondrial DNAs resembling bacterial genomes in miniature. In the first five years of our program, we propose to investigate to which degree mitochondrial information processing, from gene via RNA to protein, resembles that of bacteria or rather 'modern' mitochondria as we known them from animals, fungi, and plants. Our approach will combine classical biochemistry, new generation genomics methodologies and bioinformatics, and provide ample multi-disciplinary training opportunities for students at all levels.