Evolutionary Genomics of Supersized Mitochondrial Genomes

描述（由申请人提供）：与其他真核生物（通常为15-60 kb）相比，植物线粒体基因组非常大且大小可变（200-2,400 kb）。值得注意的是，植物中大多数不正常的大小范围都包含在一个单一的家族中，葫芦科，其线粒体基因组的大小从330到2400 kb不等。植物线粒体基因组学中一个常见且令人沮丧的主题是，绝大多数的大小变化是由于大量的基因间DNA与已知序列没有可识别的同源性。葫芦也是如此，其中65-87%的线粒体DNA （mtDNA）来源不明。发现这些神秘序列的来源是线粒体基因组学的主要挑战之一，也是本项目的主要目标。除了确定这些序列的来源，进一步的目标是确定促进植物线粒体基因组生长的一般过程。最近的一项研究提出，相似的群体遗传过程支配着核和细胞器基因组大小的进化，并得出结论，植物和动物之间线粒体基因组大小的差异反映了它们的线粒体突变率的巨大差异。也就是说，植物线粒体基因组中大量的非编码序列归因于植物mtDNA中几乎普遍存在的低突变率。通过扩展，最大的葫芦线粒体基因组预计具有最低的核苷酸取代率。该项目的数据将为这一假设提供第一个实证检验。葫芦科提供了一个令人兴奋的机会，既解决长期存在的问题，在植物线粒体基因组学和测试具有争议的新假设在广义上的基因组进化。我建议对6-10株葫芦植物的线粒体基因组进行全面测序，并使用一套互补的实验和生物信息学方法来测试关于这些特殊线粒体基因组扩张和收缩的明确假设。除了促进NIH的使命，促进创造性的科学发现和扩大我们的基础科学知识基础，该项目对线粒体基因组学领域具有更广泛的意义。在人类中，线粒体DNA突变会阻碍能量的产生，并导致许多与年龄有关的疾病。这些mtDNA突变在动物体内的积累速度比在植物体内快50- 100倍！因此，充分了解这种差异有助于我们理解与年龄有关的疾病。像这样的比较基因组研究提供了一种强大而有效的方法来描述“令人羡慕的”基因组特性（例如，植物极低的核苷酸替代率），并确定其背后的过程。

DESCRIPTION (provided by applicant): Plant mitochondrial genomes are extremely large and variably sized (200-2,400 kb) compared to other eukaryotes (typically 15-60 kb). Remarkably, most of the inordinate size range in plants is encompassed by a single family, the Cucurbitaceae, whose mitochondrial genomes vary in size from 330 to 2,400 kb. One common and frustrating theme in plant mitochondrial genomics is that the overwhelming majority of size variation is due to large amounts of intergenic DNA with no identifiable homology to known sequences. This is also true in cucurbits, where 65-87% of the mitochondrial DNA (mtDNA) is of unknown origin. Discovering the source of these enigmatic sequences is one of the major challenges in mitochondrial genomics and represents a primary goal of this project. Beyond identifying the source of these sequences, a further goal is to identify the general processes facilitating the growth of plant mitochondrial genomes. A recent study proposed that similar population genetic processes govern the evolution of nuclear and organellar genome size and concluded that the disparity in mitochondrial genome size between plants and animals reflects their drastically different mitochondriaI mutation rates. That is, the vast amounts of noncoding sequence in plant mitochondrial genomes owe to the near-universally low mutation rate observed in plant mtDNA. By extension, the largest cucurbit mitochondrial genomes are predicted to have the lowest nucleotide substitution rates. Data from this project will provide the first empirical test of this hypothesis. The Cucurbitaceae offer an exciting opportunity both to address longstanding problems in plant mitochondrial genomics and to test provocative new hypotheses on genome evolution in the broad sense. I propose to fully sequence the mitochondrial genomes for 6-10 cucurbit plants and use a complementary set of experimental and bioinformatic approaches to test explicit hypotheses about the expansion and contraction of these exceptional mitochondrial genomes. In addition to forwarding the NIH mission to foster creative scientific discovery and expand our basic scientific knowledge base, this project has broader significance to the field of mitochondrial genomics. In humans, mitochondrial DNA mutations retard energy production and contribute to a number of age-related diseases. These mtDNA mutations accumulate 50- 100 faster in animals than in plants! Therefore, a full understanding of this disparity could benefit our understanding of age-related disease and illness. Comparative genomic studies like this one provide a powerful and efficient way to characterize "enviable" genomic properties (i.e., the extraordinarily low nucleotide substitution rate of plants) and identify the processes that underlie them.