Dosage compensation can buffer copy-number variation in wild yeast.
Dosage compensation can buffer copy-number variation in wild yeast.
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DOI：
10.7554/elife.05462
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发表时间：
2015-05-08
期刊：
影响因子：
7.7
通讯作者：
Gasch AP
中科院分区：
文献类型：
--
作者：
Hose J;Yong CM;Sardi M;Wang Z;Newton MA;Gasch AP
非整倍性与无数疾病有关，但也促进了生物体的进化。目前尚不清楚细胞如何克服非整倍体的有害影响，直到新的表型进化。虽然实验室菌株是非常敏感的非整倍体，我们在这里表明，非整倍体是常见的野生酵母菌株，这表明在许多扩增基因的表达低于预期。我们生成了二倍体菌株面板，其中细胞携带两个，三个或四个受影响染色体的拷贝，以表明基因剂量补偿功能在>30%的扩增基因中发挥作用。在野生种群中，受到剂量补偿的基因表达受到更高的限制，但它们的基因扩增率升高，这表明这些基因的拷贝数变异得到了缓冲。我们发现，非整倍体提供了一个明确的生态优势，橡树株YPS1009，通过扩增的因果基因，逃脱剂量补偿。我们的工作提出了一个模型，其中剂量补偿缓冲基因扩增通过非整倍体提供一个自然的，但可能是短暂的，快速表型进化的途径。DOI：http://dx.doi.org/10.7554/eLife.05462.001进化是由生物体DNA中发现的基因和其他遗传信息的变化驱动的。例如，这些变化可能会改变生物体的物理特征，或者改变细胞内执行关键任务的效率。无论是什么变化，如果它使生物体更容易生存和繁殖，它就更有可能传递给后代。DNA在细胞内以称为染色体的结构组织起来。动物、植物和真菌中的大多数细胞含有两个染色体拷贝。然而，在细胞分裂过程中有时会发生错误，染色体的额外拷贝以及其中包含的基因可能会最终进入细胞。这些额外的基因副本可能有助于加快物种进化的速度，因为“备用”副本可以自由地适应新的角色。然而，拥有额外的基因拷贝也往往是有害的，在人类中可能导致遗传疾病，如唐氏综合症。在实验室中，染色体通常在一种称为酿酒酵母的酵母中进行研究。这个物种由几个群体或品系组成，这些群体或品系在遗传上彼此不同。多年来，为实验而培育酵母已经创造出实验室菌株，这些菌株已经失去了野生菌株中的一些特征。早期的研究表明，如果这些细胞含有额外的染色体拷贝，它们就不能正常生长。现在，Hose等人已经研究了近50种野生酿酒酵母菌株。在这些细胞中，额外的染色体拷贝是很常见的，而且似乎对生长没有不利影响。相反，Hose等人发现，具有太多基因拷贝的细胞使用这些基因中的许多基因的频率低于预期。这个过程被称为“剂量补偿”。在实验室菌株中没有观察到这种剂量补偿，部分原因是额外的基因拷贝使它们生病，难以研究。总之，这些结果提供了剂量补偿如何通过减少重复基因的负面影响来帮助物种进化新性状的例子。这些知识可能有广泛的应用，从建议减轻人类疾病的方法到暗示在酵母和其他微生物中设计有用特性的新方法。DOI：http://dx.doi.org/10.7554/eLife.05462.002网站
Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at >30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution. DOI: http://dx.doi.org/10.7554/eLife.05462.001 Evolution is driven by changes to the genes and other genetic information found in the DNA of an organism. These changes might, for example, alter the physical characteristics of the organism, or change how efficiently crucial tasks are carried out inside cells. Whatever the change, if it makes it easier for the organism to survive and reproduce, it is more likely to be passed on to future generations. DNA is organized inside cells in structures called chromosomes. Most of the cells in animals, plants, and fungi contain two copies of each chromosome. However, sometimes mistakes happen during cell division and extra copies of a chromosome—and hence the genes contained within it—may end up in a cell. These extra copies of genes might help to speed up the rate at which a species evolves, as the ‘spare’ copies are free to adapt to new roles. However, having extra copies of genes can also often be harmful, and in humans can cause genetic disorders such as Down syndrome. In the laboratory, chromosomes are commonly studied in a species of yeast called Saccharomyces cerevisiae. This species consists of several groups—or strains—that are genetically distinct from each other. Over the years, breeding the yeast for experiments has created laboratory strains that have lost some of the characteristics seen in wild strains. Earlier studies suggested that these cells fail to grow properly if they contain extra copies of chromosomes. Now, Hose et al. have studied nearly 50 wild strains of Saccharomyces cerevisiae. In these, extra copies of chromosomes are commonplace, and seemingly have no detrimental effect on growth. Instead, Hose et al. found that cells with too many copies of a gene use many of those genes less often than would be expected. This process is known as ‘dosage compensation’. This dosage compensation has not been observed in laboratory strains, in part because the extra gene copies make them sickly and hard to study. Together, the results provide examples of how dosage compensation could help new traits to evolve in a species by reducing the negative effects of duplicated genes. This knowledge may have broad application, from suggesting methods to alleviate human disorders to implicating new ways to engineer useful traits in yeast and other microbes. DOI: http://dx.doi.org/10.7554/eLife.05462.002