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首页> 外文期刊>Nucleic Acids Research >Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network
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Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network

机译：酿酒酵母基因组中未开发的必需区域的全基因组图谱：遗传相互作用网络中隐藏的合成致死组合的证据

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摘要

Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. Here, we attempted to delete these regions by PCR-mediated chromosomal deletion technology (PCD), which enables chromosomal segments to be deleted by a one-step transformation. Thirty-three of the 110 regions could be deleted, but the remaining 77 regions could not. To determine whether the 77 undeletable regions are essential, we successfully converted 67 of them to mini-chromosomes marked with URA3 using PCR-mediated chromosome splitting technology and conducted a mitotic loss assay of the mini-chromosomes. Fifty-six of the 67 regions were found to be essential for cell growth, and 49 of these carried co-lethal gene pair(s) that were not previously been detected by synthetic genetic array analysis. This result implies that regions harboring only nonessential genes contain unidentified synthetic lethal combinations at an unexpectedly high frequency, revealing a novel landscape of genetic interactions in the S. cerevisiae genome. Furthermore, this study indicates that segmental deletion might be exploited for not only revealing genome function but also breeding stress-tolerant strains.
机译：尽管对酿酒酵母中的遗传相互作用的网络作图有系统的方法，但是在全基因组范围内对遗传相互作用的探索是有限的。酿酒酵母单倍体基因组具有110个区域，这些区域长于10 kb，但仅包含非必需基因。在这里，我们尝试通过PCR介导的染色体删除技术（PCD）删除这些区域，该技术使染色体片段可以通过一步转化来删除。可以删除110个区域中的33个，但不能删除其余77个区域。为了确定77个不可删除区域是否必不可少，我们使用PCR介导的染色体分裂技术成功地将其中67个不可转换区域转化为标记为URA3的微型染色体，并对微型染色体进行了有丝分裂损失分析。 67个区域中有56个区域对于细胞生长至关重要，其中49个区域带有先前未通过合成遗传阵列分析检测到的共致死基因对。该结果暗示仅包含非必需基因的区域以意外的高频率包含未鉴定的合成致死组合，揭示了酿酒酵母基因组中遗传相互作用的新情况。此外，这项研究表明，节段缺失不仅可以用于揭示基因组功能，还可以用于育种耐胁迫菌株。

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