Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):21010-5. doi: 10.1073/pnas.1211150109. Epub 2012 Nov 29.
Aneuploidy, an abnormal number of chromosomes, is a widespread phenomenon found in unicellulars such as yeast, as well as in plants and in mammalians, especially in cancer. Aneuploidy is a genome-scale aberration that imposes a severe burden on the cell, yet under stressful conditions specific aneuploidies confer a selective advantage. This dual nature of aneuploidy raises the question of whether it can serve as a stable and sustainable evolutionary adaptation. To clarify this, we conducted a set of laboratory evolution experiments in yeast and followed the long-term dynamics of aneuploidy under diverse conditions. Here we show that chromosomal duplications are first acquired as a crude solution to stress, yet only as transient solutions that are eliminated and replaced by more efficient solutions obtained at the individual gene level. These transient dynamics of aneuploidy were repeatedly observed in our laboratory evolution experiments; chromosomal duplications gained under stress were eliminated not only when the stress was relieved, but even if it persisted. Furthermore, when stress was applied gradually rather than abruptly, alternative solutions appear to have emerged, but not aneuploidy. Our findings indicate that chromosomal duplication is a first evolutionary line of defense, that retains survivability under strong and abrupt selective pressures, yet it merely serves as a "quick fix," whereas more refined and sustainable solutions take over. Thus, in the perspective of genome evolution trajectory, aneuploidy is a useful yet short-lived intermediate that facilitates further adaptation.
非整倍体,即染色体数目异常,是一种广泛存在的现象,不仅在单细胞生物如酵母中,也在植物和哺乳动物中,特别是在癌症中存在。非整倍体是一种基因组规模的畸变,会给细胞带来严重负担,但在应激条件下,特定的非整倍体赋予了选择优势。非整倍体的这种双重性质引发了一个问题,即它是否可以作为一种稳定且可持续的进化适应。为了阐明这一点,我们在酵母中进行了一系列实验室进化实验,并在不同条件下跟踪了非整倍体的长期动态。在这里,我们表明染色体加倍最初是作为一种应对应激的粗糙解决方案获得的,但只是作为瞬时解决方案,会被个体基因水平上获得的更有效的解决方案所消除和取代。这些非整倍体的瞬态动力学在我们的实验室进化实验中反复出现;在应激下获得的染色体加倍不仅在应激缓解时被消除,即使应激持续存在时也会被消除。此外,当应激逐渐施加而不是突然施加时,似乎出现了替代解决方案,但不是非整倍体。我们的研究结果表明,染色体加倍是第一道进化防线,它在强烈和突然的选择压力下保持生存能力,但它只是一种“快速修复”,而更精细和可持续的解决方案则取而代之。因此,从基因组进化轨迹的角度来看,非整倍体是一种有用但短暂的中间状态,有助于进一步适应。