Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast.
Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast.
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DOI：
10.1038/nature09529
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发表时间：
2010-11-11
期刊：
影响因子：
64.8
通讯作者：
Li, Rong
中科院分区：
文献类型：
--
作者：
Pavelka, Norman;Rancati, Giulia;Zhu, Jin;Bradford, William D.;Saraf, Anita;Florens, Laurence;Sanderson, Brian W.;Hattem, Gaye L.;Li, Rong
非整倍性，这里指的是以染色体数目异常为特征的基因组内容，与实验生物的发育缺陷、癌症和适应性进化有关。然而，非整倍体如何影响基因表达，以及非整倍体是否能直接带来表型变异并改善整倍体的适应性，仍是一个悬而未决的问题。在这项工作中，我们设计了一种新的方案，通过随机减数分裂分离，38个稳定的和完全等基因的非整倍体酵母菌株具有不同的核型和基因组含量之间的1N和3N，而不涉及任何遗传选择。通过在各种生长条件下或在存在一组化疗或抗真菌药物的情况下进行表型分析，我们发现非整倍体菌株表现出不同的生长表型，并且一些非整倍体菌株在次优条件下比整倍体对照菌株生长得更好。使用定量质谱为基础的蛋白质组学，我们表明，蛋白质的表达水平在很大程度上与染色体拷贝数的比例，以下相同的趋势观察到的转录组。这些结果提供了强有力的证据表明，非整倍性直接影响转录组和蛋白质组水平的基因表达，并可以产生显着的表型变异，可以在不同的条件下带来健身收益。我们的研究结果表明，整倍体和非整倍体细胞之间的健身排名是上下文和核型依赖，提供了基础的概念，非整倍体可以直接表型进化和细胞适应。
Aneuploidy, referring here to genome contents characterized by abnormal numbers of chromosomes, has been associated with developmental defects, cancer, and adaptive evolution in experimental organisms. However, it remains unresolved how aneuploidy impacts gene expression and whether aneuploidy could directly bring phenotypic variation and improved fitness over that of euploid counterparts. In this work, we designed a novel scheme to generate, through random meiotic segregation, 38 stable and fully isogenic aneuploid yeast strains with distinct karyotypes and genome contents between 1N and 3N without involving any genetic selection. Through phenotypic profiling under various growth conditions or in the presence of a panel of chemotherapeutic or antifungal drugs, we found that aneuploid strains exhibited diverse growth phenotypes, and some aneuploid strains grew better than euploid control strains under conditions suboptimal for the latter. Using quantitative mass spectrometry-based proteomics, we show that the levels of protein expression largely scale with chromosome copy numbers, following the same trend observed for the transcriptome. These results provide strong evidence that aneuploidy directly impacts gene expression at both the transcriptome and proteome levels and can generate significant phenotypic variation that could bring about fitness gains under diverse conditions. Our findings suggest that the fitness ranking between euploid and aneuploid cells is context- and karyotype-dependent, providing the basis for the notion that aneuploidy can directly underlie phenotypic evolution and cellular adaptation.
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影响因子：
46.9
作者：
Washburn, MP;Wolters, D;Yates, JR
通讯作者：
Yates, JR
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G
DOI：
10.1007/bf00330602
发表时间：
1988-02-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
MACK, M;GOMPELKLEIN, P;BRENDEL, M
通讯作者：
BRENDEL, M
影响因子：
56.9
作者：
Williams, Bret R.;Prabhu, Vineet R.;Amon, Angelika
通讯作者：
Amon, Angelika