Bonney Megan E, Moriya Hisao, Amon Angelika
Koch Institute for Integrative Cancer Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
Research Core for Interdisciplinary Sciences, Okayama University, Okayama 700-8530, Japan.
Genes Dev. 2015 May 1;29(9):898-903. doi: 10.1101/gad.261743.115.
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.
非整倍体——即一条或多条整条染色体的增加或减少——通常会对生物体的适应性产生不利影响，如在唐氏综合征等病症中表现出来。一个核心问题是，非整倍体表型是少数可能存在于额外染色体上的特别有害基因的拷贝数变化的结果，还是由许多单个基因拷贝数改变（单个基因改变时不产生可观察到的表型）导致的。我们利用携带单条额外染色体（双体）的芽殖酵母菌株所表现出的增殖缺陷，来区分“少数关键基因”假说和“基因的群体作用”假说。我们的结果表明，整条染色体上基因剂量的细微变化可能会产生显著的表型后果。我们得出结论，拷贝数变化的群体作用可以跨越表型阈值，而这些拷贝数变化本身是无害的。
