A genome-wide map of mitochondrial DNA recombination in yeast.
A genome-wide map of mitochondrial DNA recombination in yeast.
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DOI：
10.1534/genetics.114.166637
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发表时间：
2014-10
期刊：
影响因子：
3.3
通讯作者：
Steinmetz LM
中科院分区：
文献类型：
--
作者：
Fritsch ES;Chabbert CD;Klaus B;Steinmetz LM
在真核细胞中，细胞能量的产生需要细胞核和线粒体基因组之间的密切相互作用。线粒体基因组是必不可少的，因为它编码了几个参与氧化磷酸化的基因。每个细胞包含几个线粒体基因组拷贝，线粒体DNA重组是一个广泛发生在植物、真菌、原生生物和无脊椎动物中的过程。酿酒酵母菌已被证明是一个很好的模型来解剖线粒体生物学。一些研究集中在这个细胞器中的DNA重组，但大多依赖于报告基因或人工系统。然而，目前还没有真核生物完整的线粒体重组图谱。在目前的工作中，我们对来自两个不同酿酒葡萄球菌菌株杂交的二倍体进行了测序，以检测重组事件。这一策略使我们能够生成首个酵母线粒体DNA重组的全基因组图谱。我们证明重组事件在特定的热点富集，优先定位于非蛋白质编码区。另外，对两个不同杂交组合的重组谱进行比较，发现遗传背景影响热点定位和重组率。最后，为了深入了解线粒体重组的机制，我们评估了先前与此过程相关的四个基因的个体缺失的影响。NTG1和MGT1的缺失并未对重组格局产生实质性影响，暗示可能存在其他调控因子。我们的研究结果还揭示了MHR1缺失时线粒体DNA大区域的缺失，这表明MHR1在交配期间线粒体基因组维持中起着关键作用。本研究提供了酵母线粒体DNA重组的全面概述，从而为未来线粒体重组和基因组维持的机制研究铺平了道路。
In eukaryotic cells, the production of cellular energy requires close interplay between nuclear and mitochondrial genomes. The mitochondrial genome is essential in that it encodes several genes involved in oxidative phosphorylation. Each cell contains several mitochondrial genome copies and mitochondrial DNA recombination is a widespread process occurring in plants, fungi, protists, and invertebrates. Saccharomyces cerevisiae has proved to be an excellent model to dissect mitochondrial biology. Several studies have focused on DNA recombination in this organelle, yet mostly relied on reporter genes or artificial systems. However, no complete mitochondrial recombination map has been released for any eukaryote so far. In the present work, we sequenced pools of diploids originating from a cross between two different S. cerevisiae strains to detect recombination events. This strategy allowed us to generate the first genome-wide map of recombination for yeast mitochondrial DNA. We demonstrated that recombination events are enriched in specific hotspots preferentially localized in non-protein-coding regions. Additionally, comparison of the recombination profiles of two different crosses showed that the genetic background affects hotspot localization and recombination rates. Finally, to gain insights into the mechanisms involved in mitochondrial recombination, we assessed the impact of individual depletion of four genes previously associated with this process. Deletion of NTG1 and MGT1 did not substantially influence the recombination landscape, alluding to the potential presence of additional regulatory factors. Our findings also revealed the loss of large mitochondrial DNA regions in the absence of MHR1, suggesting a pivotal role for Mhr1 in mitochondrial genome maintenance during mating. This study provides a comprehensive overview of mitochondrial DNA recombination in yeast and thus paves the way for future mechanistic studies of mitochondrial recombination and genome maintenance.