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大规模研究揭示基因组结构与稳定性
2019-09-12 15:54

英国剑桥大学Stephen P. Jackson、Fabio Puddu等研究人员合作,剖析了酿酒酵母基因敲除收集库中基因组的结构与稳定性。2019年9月11日,《自然》在线发表了这一成果。

研究人员表示,尽管人们在定义基因的功能作用方面取得了重大进展,但即使在相对简单的生物体中,对其影响的完全理解还远未实现。酿酒酵母基因敲除收集库(YKOC)的完成是这个方向的一个重要里程碑,该收集库能够用于高通量反向遗传学、表型筛选和合成-遗传相互作用分析。随后的实验工作也突显出了YKOC中的一些不一致和错误,或者基因组不稳定事件(对特定基因敲除的效果进行重新平衡),但缺乏这些问题的完整描述。维持基因组稳定性所需基因的鉴定和分析在传统上依赖于报告基因检测和单个基因缺失的研究,但现在全基因组测序技术能够在全局范围内直接观察基因组不稳定性。

鉴于此,研究人员对几乎所有包含纯合二倍体YKOC的4732个菌株的全基因组进行了测序。通过提取串联和散布重复DNA元件的拷贝数变异信息,研究人员描述了几乎每一个非必需基因中由其丢失引起的基因组改变。对该数据集的分析揭示了影响各种基因组元件维持的基因,突出了核与线粒体基因组稳定性之间的交叉对话,并显示了在没有单个非必需基因的情况下菌株如何在遗传上适应生存。

附:英文原文

Title:Genome architecture and stability in the Saccharomyces cerevisiae knockout collection

Author:Fabio Puddu, Mareike Herzog, Alexandra Selivanova, Siyue Wang, Jin Zhu, Shir Klein-Lavi, Molly Gordon, Roi Meirman, Gonzalo Millan-Zambrano, Iñigo Ayestaran, Israel Salguero, Roded Sharan, Rong Li, Martin Kupiec, Stephen P. Jackson

Issue&Volume: 2019-09-11

Abstract:

Despite major progress in defining the functional roles of genes, a complete understanding of their influences is far from being realized, even in relatively simple organisms. A major milestone in this direction arose via the completion of the yeast Saccharomyces cerevisiae gene-knockout collection (YKOC), which has enabled high-throughput reverse genetics, phenotypic screenings and analyses of synthetic-genetic interactions1,2,3. Ensuing experimental work has also highlighted some inconsistencies and mistakes in the YKOC, or genome instability events that rebalance the effects of specific knockouts4,5,6, but a complete overview of these is lacking. The identification and analysis of genes that are required for maintaining genomic stability have traditionally relied on reporter assays and on the study of deletions of individual genes, but whole-genome-sequencing technologies now enable—in principle—the direct observation of genome instability globally and at scale. To exploit this opportunity, we sequenced the whole genomes of nearly all of the 4,732 strains comprising the homozygous diploid YKOC. Here, by extracting information on copy-number variation of tandem and interspersed repetitive DNA elements, we describe—for almost every single non-essential gene—the genomic alterations that are induced by its loss. Analysis of this dataset reveals genes that affect the maintenance of various genomic elements, highlights cross-talks between nuclear and mitochondrial genome stability, and shows how strains have genetically adapted to life in the absence of individual non-essential genes.

DOI: 10.1038/s41586-019-1549-9

Source: https://www.nature.com/articles/s41586-019-1549-9

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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