Aneuploid proliferation defects in yeast are not driven by copy number changes of a few dosage-sensitive genes.
Aneuploid proliferation defects in yeast are not driven by copy number changes of a few dosage-sensitive genes.
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DOI：
10.1101/gad.261743.115
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发表时间：
2015-05-01
影响因子：
10.5
通讯作者：
Amon A
中科院分区：
文献类型：
--
作者：
Bonney ME;Moriya H;Amon A
一个中心问题是，非整倍体表型是否是可能存在于额外染色体上的一些特别有害的基因的拷贝数变化的结果，或者是由许多基因的拷贝数改变引起的，这些基因在单独变化时没有可观察到的表型。Bonney等人使用携带单个额外染色体（二体）的芽殖酵母菌株所表现出的增殖缺陷来表明，染色体上基因剂量的细微变化可能具有显著的表型后果。非整倍性--一个或多个完整染色体的获得或丢失--通常对生物体的健康有不利影响，表现在唐氏综合症等疾病中。一个中心问题是，非整倍体表型是否是可能存在于额外染色体上的一些特别有害的基因的拷贝数变化的结果，或者是由许多基因的拷贝数改变引起的，这些基因在单独变化时没有可观察到的表型。我们使用的芽殖酵母菌株携带单个额外的染色体（二体）表现出的增殖缺陷，以区分“少数关键基因”假说和“基因的大规模行动”假说。我们的研究结果表明，基因剂量在染色体上的细微变化可以有显着的表型后果。我们的结论是，表型阈值可以跨越的大规模行动的拷贝数的变化，就其本身而言，是良性的。
A central question is whether aneuploid phenotypes are the consequence of copy number changes of a few especially harmful genes that may be present on the extra chromosome or are caused by copy number alterations of many genes that confer no observable phenotype when varied individually. Bonney et al. used the proliferation defect exhibited by budding yeast strains carrying single additional chromosomes (disomes) to show that subtle changes in gene dosage across a chromosome can have significant phenotypic consequences. Aneuploidy—the gain or loss of one or more whole chromosome—typically has an adverse impact on organismal fitness, manifest in conditions such as Down syndrome. A central question is whether aneuploid phenotypes are the consequence of copy number changes of a few especially harmful genes that may be present on the extra chromosome or are caused by copy number alterations of many genes that confer no observable phenotype when varied individually. We used the proliferation defect exhibited by budding yeast strains carrying single additional chromosomes (disomes) to distinguish between the “few critical genes” hypothesis and the “mass action of genes” hypothesis. Our results indicate that subtle changes in gene dosage across a chromosome can have significant phenotypic consequences. We conclude that phenotypic thresholds can be crossed by mass action of copy number changes that, on their own, are benign.
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